Carbopeptoids and carbonucleotoids

ABSTRACT

Libraries are synthesized with oligomeric carbopeptoids and carbonucleotoids. Carbopeptoids are oligosaccharides having carbohydrate subunits linked to one another by amide bonds. Carbonucleotoids are oligosaccharides having carbohydrate subunits linked to one another by phosphodiester bonds. Carbopeptoid libraries may be fabricated using automated polypeptide synthesizers. Carbonucleotoid libraries may be fabricated using automated polynucleotide synthesizers.

SPECIFICATION

[0001] 1. Field of the Invention

[0002] The invention relates to oligosaccharides and librariesincorporating oligosaccharide. More particularly, the invention relatesto oligosaccharides and libraries of oligosaccharides which employ amideand/or phosphodiester linkages for joining adjacent carbohydratesubunits.

[0003] 2. BACKGROUND

[0004] Carbohydrates are known to mediate many cellular recognitionprocesses. Carbohydrates can serve directly as binding molecules and, insuch instances, are essential to the recognition process. A review ofthe biological role of carbohydrates with respect to cellularrecognition phenomena is provided by Sharon et al. (Scientific American,Jan. 1993, 82). The emerging importance of glycobiology is furthercharacterized by Mekelburger et al. (Angew. Chem. Int. Ed. Engl. 1992,31, 1571) and by Dagani et al. (Chem. Eng. News, Feb. 1, 1993, 28).

[0005] Dysfunctional mediation of cellular recognition processes canlead to disease states. If a cellular recognition process is mediated byan oligosaccharide, then an absence or excess of such oligosaccharidecan lead to a dysfunctional mediation of such process. The mediatingoligosaccharide may be deficient or absent due to a deficiency ofproduction or due to a high rate of catabolism. If rate of catabolism isexcessive, then catabolically resistant analogs of the bioactiveoligosaccharide may be preferred as drug candidates as compared to thenative bioactive oligosaccharide.

[0006] Accordingly, what is needed is a library which includes analogsof known bioactive oligosaccharides. Such a library may be usefullyemployed for screening drug candidates.

[0007] Central requirements for the design of libraries ofoligosaccharide analogs include the following:

[0008] (a) A need to maximize the potential of the designedoligosaccharides as ligand and drug candidates;

[0009] (b) A need to capitalize on existing highly sophisticatedtechnology directed to the synthesis of oligopeptides andoligonucleotides in order to facilitate the rapid and efficient designand construction of oligosaccharides; and

[0010] (c) A need for flexibility with respect to synthesizing eithersingle target molecules or large libraries of target moleculessimultaneously.

[0011] Methodologies for synthesizing biopolymers are well developed forpeptides, nucleic acids, and saccharides. Segments of oligopeptides andof oligonucleotides can now be routinely synthesized both in solutionand in the solid phase, manually and/or on automated systems. Thesynthesis of such structures is facilitated by the availability ofefficient techniques and sophisticated instrumentation for synthesizingpeptide and phosphate bonds with high yields. The synthesis ofoligopeptides and oligonucleotides is also facilitated by the absence ofstereocenters in these linkages. In contrast, technology for theconstruction of oligosaccharides is comparatively less sophisticated andefficient. Synthetic methods for constructing oligosaccharides givecomparatively lower yields and are complicated by the two isomerpossibilities (α and β) in glycoside bond formation.

[0012] Techniques and chemical methods for simultaneously synthesizingmultiple oligopeptides, e.g. 100-150 completely different peptideshaving lengths of up to 20 amino acid residues, are reviewed by Jung, G.et al. (Angew. Chem, Int. Ed. Engl. 1992, 31, 367-383 -incorporatedtherein by reference). Such techniques facilitate the construction ofoligopeptide libraries.

[0013] Simon, et al. (Proc, Natl. Acad. Sci. USA, 1992, 89, 9367-9371)disclose oligopeptide analogs in which amino acid side chain groups areattached not to conventional peptide backbone carbons but to peptidebackbone nitrogens. Such analogs are termed peptoids. Simon alsodiscloses the construction of peptoid libraries as a modular approach todrug discovery. Simon's oligopeptoids are shown by calculation to havegreater conformational freedom as compared to conventionaloligopeptides. Accordingly, oligopeptoids are thought to have greaterpotential as pharmaceutically useful binding ligands as compared toconventional oligopeptides having close sequence homology to sucholigopeptoids.

[0014] Von Roedern et al. disclose a carbohydrate amino acid (Angew.Chem, Int. Ed. Engl. 1994, 31, 687-689). Although von Roedern disclosesthat carbohydrate amino acids may be coupled to peptides, he does notdisclose that they may also be polymerized so as to formoligosaccharides.

SUMMARY

[0015] A first aspect of the invention involves the molecular design andchemical synthesis of a class of carbohydrates designated ascarbopeptoids (CPD's). Glycopeptoids are preferred carbopeptoids.Carbopeptoids and glcopeptoids are oligosaccharides which employpeptide-like amide bonds for linking the various carbohydrate subunitswithin an oligomer assembly. Amide bond formation may be achieved byemploying oligopeptide synthesis technology and instrumentation. Themethod allows for the design and synthesis of specific compounds forbiological and pharmacological investigations. The method also allowsfor the generation of libraries of compounds for biological andpharmacological screening. Conventional screening techniques employedwith respect to peptide and peptoid libraries (Simon et al., supra) mayalso be employed with respect to carbopeptoid libraries. The designtakes advantage of the multifunctionality of carbohydrate subunits tomaximize the binding properties of the molecules. The ease and highefficiency by which the peptide-like linkages can be constructed makethe synthesis of these molecules a practical proposition. Furthermore,non-carbohydrate units may be inserted into the sequence making thisapproach even more flexible and versatile for the generation of newlibraries of organic compounds.

[0016] More particularly, the invention is directed to a oligomericcarbopeptoid or glycopeptoid compound having carbohydrate amino acidsubunits (CA's) or glycoside amino acid subunits (GA's) coupled to oneanother via an amide linkage. The amide linkage may be represented bythe formula CA₁—(CO—NH)—CA₂. The amide linkage (CO—NH) includes acarbonyl carbon and an amido nitrogen. A first carbohydrate amino acidsubunit CA₁ or glycoside amino acid subunit GA₁ has an anomeric carbonbonded to the carbonyl carbon of the amide linkage. The anomeric carbonof the first carbohydrate amino acid subunit CA₁ forms a C-glycosidicbond with the carbonyl carbon of the amide linkage and maintains thecarbohydrate in a closed ring configuration. A second carbohydrate aminoacid subunit CA₂ has a non-anomeric carbon bonded to the amido nitrogenof the amide linkage. The second carbohydrate amino acid subunit CA₂,like the first amino acid subunit CA₁, may include an anomeric carbonbonded to the carbonyl carbon of a second amide linkage linking thesecond carbohydrate amino acid subunit CA₂ to a third carbohydrate aminoacid subunit CA₃, etc. In this instance, the anomeric carbon of thesecond carbohydrate amino acid subunit CA₂ forms a C-glycosidic bondwith the carbonyl carbon of the amide linkage and maintains thecarbohydrate in a closed ring configuration. On the other hand, if thesecond carbohydrate amino acid subunit CA₂ is a terminal subunit, thenits anomeric carbon may form a hemiacetal, a hemiketal, or a glycoside.

[0017] The invention is also directed to a process for synthesizing theabove oligomeric carbopeptoid or glycopeptoid compound. The syntheticprocess involves the coupling of two or more carbohydrate amino acidsubunits (CA's) or glycoside amino acid subunits (GA's) to one anotherby means of amide linkages.

[0018] The invention is also directed to libraries of oligomericcarbopeptoid or glycopeptoid compounds. Such libraries are employablefor drug screening. Each oligomeric carbopeptoid or glydopeptoidcompound includes at least two carbohydrate amino acid subunits (CA's)or glycoside amino acid subunits (GA's) coupled to one another via anamide linkage as indicated above. The invention is also directed to animproved process for synthesizing the above library of oligomers. Theprocess employs an elongation step for coupling the subunits to oneanother to produce the oligomers. In the elongation step, twocarbohydrate amino acid subunits (CA's) or glycoside amino acid subunits(GA's) are coupled to one another via an amide linkage as indicatedabove.

[0019] The invention is also directed to chemical intermediates forproducing oligomeric carbopeptoids. A first chemical intermediate is aderived carbohydrate amino acid having an anomeric carbon andnon-anomeric carbons. The anomeric carbon is substituted with a carboxylradical. Each of the non-anomeric carbons is substituted with a radicalselected from the group consisting of blocked hydroxyl, blocked amino,differentially protected amino, and hydrogen, with the proviso that atleast one radical is a differentially protected amino. A second chemicalintermediate is a derived carbohydrate amino acid similar to the firstexcept that the non-anomeric carbons are substituted with a radicalselected from the group consisting of blocked hydroxyl, blocked amino,unprotected amino, and hydrogen, with the proviso that at least oneradical is an unprotected amino and at least one radical is a blockedhydroxyl or amino.

[0020] A second aspect of the invention involves the molecular designand chemical synthesis of a class of carbohydrates designated ascarbonucleotoids (CND's). Carbonucleotoids are oligosaccharides whichemploy oligonucleotide-like phosphate bonds for linking the variouscarbohydrate subunits within an oligomer assembly. Phosphate bondformation may be achieved by employing technology and instrumentationdeveloped for oligonucleotide synthesis. The phosphate bonds employedwithin carbonucleotoids are convenient linkages for coupling theseunits. The ease and high efficiency by which the oligonucleotide-likelinkages can be constructed make the synthesis of these molecules apractical proposition.

[0021] The disclosed methods are characterized by their versatility andpracticality. The methods may exploit conventional solid phase andautomated synthesis techniques for producing carbopeptoids andcarbonucleotoids in large scale.

[0022] More particularly, the second aspect of the invention is directedto an oligomeric carbonucleotoid molecule comprising carbohydrateC-glycoside subunits (CG's) coupled to one another via a phosphodiesterlinkage. The phosphodiester linkage may be represented by the structure:CG₁—C₁—(O—PO(OH)—O)—CG₂. The first carbohydrate C-glycoside subunit(CG₁—C₁) has an anomeric carbon forming a C-glycosidic bond with acarbon C₁. In turn the carbon C₁ is bonded to the phosphodiesterlinkage. The second carbohydrate C-glycoside subunit CG2 has anon-anomeric carbon bonded to the phosphodiester linkage. The inventionis also directed a process for synthesizing the oligomericcarbonucleotoid molecule. The process employs a coupling step whereintwo or more carbohydrate C-glycoside subunits (CG's) are coupled bymeans of a phosphodiester linkage as indicated above.

[0023] The second aspect of the invention is also directed to librariesof oligomeric carbonucleotoid molecules. The libraries are employablefor drug screening. Each oligomeric carbonucleotoid molecule includingat least two carbohydrate C-glycoside subunits (CG's) coupled to oneanother by means of a phosphodiester linkage as indicated above. Theinvention is also directed to an improved process for synthesizing alibrary of oligomers. The process employs an elongation step whereinsubunits are coupled to one another to produce the oligomers. Theimprovement is directed to the use of phosphodiester linkage linkagesfor linking the C-glycoside subunits as indicated above.

[0024] The second aspect of the invention is also directed to derivedcarbohydrate C-glycosides having an anomeric carbon and non-anomericcarbons. The anomeric carbon forms a C-glycosidic bond with carbon C₁.In turn, the carbon C₁ is bonded to an phosphoramidite. Each of thenon-anomeric carbons is substituted with a radical selected from thegroup consisting of blocked hydroxyl, differentially protected hydroxyl,and hydrogen, with the proviso that at least one radical is adifferentially protected hydroxyl. An alternative derived carbohydrateC-glycoside is similar to the above except that each of the non-anomericcarbons is substituted with a radical selected from the group consistingof blocked hydroxyl, unprotected hydroxyl, and hydrogen, with theproviso that at least one radical is an unprotected hydroxyl and atleast one radical is a blocked hydroxyl.

DETAILED DESCRIPTION

[0025] Retrosynthetic schemes for carbopeptoids (compound I) andcarbonucleotoids (compound II) are illustrated in Scheme 1.

[0026] The carbopeptoids (CPD's) are oligomers having repeatingcarbohydrate subunits linked to one another by means of amide linkageunits. More particularly, the carbonyl carbon of each amide linkage unitis bonded to the anomeric carbon of a carbohydrate subunit. Similarly,the amide nitrogen of the amide linkage unit is bonded to a non-anomericcarbon. The retrosynthetic scheme suggests that the amide bond may besplit and that the preferred starting materials are carbohydrate aminoacids.

[0027] Carbonucleotoids (CND's) are oligosaccharides in whichcarbohydrate C-glycoside subunits (CG's) are linked to one another bymeans of phosphodiester bonds. More particularly, the retrosyntheticscheme suggests that the phosphate group may be eliminated, yieldinghydroxylated starting material.

[0028] Scheme 2 illustrates representative carbohydrate amino acidsubunits (CA's) and carbohydrate C-glycoside subunits (CG's). Preferredcarbohydrate amino acid subunits (CA's) include the following:

[0029] D-glucose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0030] D-mannose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0031] D-galactose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0032] N-acetyl-D-glucosamine having an unprotected carboxyl at theanomeric C1) position, an unprotected amino group at the C(6) position,a blocked amino group at the C(2) position, and blocked hydroxyls at theC(3) and C(4) positions;

[0033] α-D-idose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0034] α-D-altrose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0035] α-D-gulose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(6) position, and blockedhydroxyls at the C(2), C(3), and C(4) positions;

[0036] α-D-glucose having an unprotected O-glycosidic amino at theanomeric C(1) position, an unprotected carboxyl as the C(6) position,and blocked hydroxyls at the C(2), C(3), and C(4) positions;

[0037] D-mannose having an unprotected O-glycosidic amino at theanomeric C(1) position, an unprotected carboxyl as the C(6) position,and blocked hydroxyls at the C(2), C(3), and C(4) positions;

[0038] D-galactose having an unprotected O-glycosidic amino at theanomeric C(1) position, an unprotected carboxyl as the C(6) position,and blocked hydroxyls at the C(2), C(3), and C(4) positions;

[0039] N-acetyl-D-glucosamine having an unprotected O-glycosidic aminoat the anomeric C(1) position, an unprotected carboxyl as the C(6)position, a blocked amino group at the C(2) position and blockedhydroxyls at the C(3) and C(4) positions;

[0040] D-ribose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(5) position, and blockedhydroxyls at the C(2) and C(3) positions; and

[0041] D-arabinose having an unprotected carboxyl at the anomeric C(1)position, an unprotected amino group at the C(5) position, and blockedhydroxyls at the C(2) and C(3) positions.

[0042] Preferred carbohydrate amino acid subunits (CA's) include thefollowing:

[0043] D-glucose having a C(1) C₁-glycosidic carbon bonded to aphosphoramidite, an unprotected hydroxyl at the C(6) position andblocked hydroxyls at the C(2), C(3), and C(4) positions;

[0044] D-mannose having a C(1) C₁-glycosidic carbon bonded to aphosphoramidite, an unprotected hydroxyl at the C(6) position andblocked hydroxyls at the C(2), C(3), and C(4) positions;

[0045] D-galactose having a C(1) C₁-glycosidic carbon bonded to aphosphoramidite, an unprotected hydroxyl at the C(6) position andblocked hydroxyls at the C(2), C(3), and C(4) positions; and

[0046] N-acetyl-D-glucosamine having a C(1) C₁-glycosidic carbon bondedto a phosphoramidite, an unprotected hydroxyl at the C(6) position, ablocked amino at the C(2) position, and blocked hydroxyls at the C(3)and C(4) positions.

[0047] Scheme 3 outlines a preferred synthesis of suitably protectedcarbohydrate amino acid subunits (CA's) from D-glucose, i.e. compound46.

[0048] Scheme 4 outlines the synthesis of suitably protectedcarbohydrate amino acid subunits (CA's) from N-acetyl-D-glucosamine,i.e. compound 62.

[0049] Scheme 5 summarizes the synthesis of hexamer 74, i.eglucose-glucosamine hetero carbopeptoid (CPD).

[0050] Scheme 6 illustrates the construction of suitably protected andactivated C-glycoside subunits (CG's) corresponding to glucose.

[0051] Scheme 7 illustrates the construction of suitably protected andactivated C-glycoside subunits (CG's) corresponding to glucosamine.

[0052] Scheme 8 summarizes the synthesis of hexamer 116, i.e.glucose-glucosamine hetero carbonucleotoid (CND).

[0053] The chemistries illustrated in Schemes 5 and 8 for synthesizingheterohexamer CPD 74 and heterohexamer CND 116 can also be employed forsynthesizing homohexamer CPD's 118 (glucose) and 120 (glucosamine) andhomohexamer CND's 122 (glucose) and 124 (glucosamine).

[0054] In analogy with the construction of oligopeptide andoligonucleotide libraries, a oligosaccharide carbopeptoid (CPD) librarymay be constructed by performing using a split synthesis method ofoligomerization as illustrated in Scheme 500 for carbopeptoids andScheme 550 for carbonucleotoids. For example, the split synthesis mayemploy beads upon which to build the oligomers. Beads are aliquoted intoeach of a several reaction vessels, each reacrtion vessel containing adifferent core molecule. The core molecules are then allowed to attachto the beads. The beads are washed, mixed with one another, and thenre-aliquoted (split) into a second set of reaction vessels for additionof a second core molecule to the first added core molecule. The processis then reiterated until the oligomerization process is complete. Theresultant library of oligosaccharides may then be screened usingconventional methods developed for oligopeptide and oligonucleotidelibraries. Screening an oligosaccharide library can lead to theidentification of individual oligosaccharide components within thelibrary having binding activity and/or bioactivity.

[0055] The above oligosaccharide libraries (CPD and CND) may be enlargedby introducing additional functionalities into the basic CA's and CG's.

[0056] The above oligosaccharide libraries (CPD and CND) may be furtherenlarged by enlarging the pool of free functional groups on the CA's andCG's and employed this enlarged pools of CA's and CG's during therespective split synthesis processes.

[0057] Scheme 20 illustrate a protocol published by Fuchs, E. F. et al.(J. Chem Ber. 1975, 108, 2254) for the synthesis of CA 45 and 46 fromglucose pentaacetate. Additionally, Scheme 20 illustrates a syntheticroute for CG 82, also starting from glucose pentaacetate. The reagentsand conditions for synthesizing CG 82 are provided as follows:

[0058] Steps (a)-(d): according to Fuchs (supra).

[0059] Step (e):

[0060] (1) DMTCl, DMAP, Pyridine; room temperature.

[0061] (2) TESTfl; 0° C.

[0062] Step (f): DIBAL—H, CH₂Cl₂; −78° C.; and

[0063] Step (g): (NCCH₂CH₂) (NiPr₂)PCl, tetrazole, CH₂Cl₂.

[0064] The reagents and conditions for synthesizing CA 46 from CA 45 areprovided in Step M as follows:

[0065] Step (m): FMOC—Cl, K₂CO₃, THF, H₂O; 0° C.

[0066] A synthetic route for producing C-glycosides (CG's) withβ-configuration at the former anomeric center is illustrated in Scheme21. The starting material (compound 36) is commercially available. Thereagents and conditions for synthesizing CG 181 and CG 185 are asfollows:

[0067] Step (a): Co₂(CO)₈, HSiEt₂Me, CO.

[0068] Step (b):

[0069] (1) AcOH, H₂O, THF;

[0070] (2) RuCl₃, NalO₄, CH₂CN, H₂O, CCL₄, room temperature;

[0071] Step (c): NaOMe, MeOH;

[0072] Step (d):

[0073] (1) DMTCl, DMAP, Pyridine, room temperature;

[0074] (2) TESOTf;

[0075] Step (e): BH₃—THF;

[0076] Step (f): (NCCH₂CH₂) (NiPr₂)PCl, tetrazole, Ch₂Cl₂;

[0077] Step (g):

[0078] (1) 1 equiv TsCl. base;,

[0079] (2) TESOTf;

[0080] Step (h): NaN₃;

[0081] Step (i): H₂, Pd(OH)₂—C;

[0082] Step (j): FMOC—Cl, base.

[0083] Synthetic routes for producing with C-glycosides withα-configurations at the former anomeric center, i.e. CG 196 and CG 1204,are illustrated in Scheme 22. The common starting material for thesesynthetic routes (compound 190) is disclosed by Schmidt, R. R. et al.(Liebigs Ann. Chem. 1987, 825). The reagents and conditions for thereactions leading to CG 196 and CG 204 are as follows:

[0084] Step (a): reductive debenzylation;

[0085] Step (b):

[0086] (1) equiv TsCl. base;

[0087] (2) TESoTf.

[0088] Step (c): NaN₃.

[0089] Step (d): RuCl₃, NalO₄, CH₃CN, H₂O, CC₄.

[0090] Step (e): H₂, Pd—C.

[0091] Step (f): FMOC—Cl, base.

[0092] Step (g):

[0093] (1) DMTCl, DMAP, Pyridine, room temperature;

[0094] (2) TESOTf.

[0095] Step (h):

[0096] (1) RuCl₃, NalO₄, CH₃CN, H₂O, CC₄;

[0097] (2) CH₂N₂.

[0098] Step (i): DIBAL—H.

[0099] Step (j): PPh₃, DIAD, diphenyl phosphoryl azide (DPPA),THF.

[0100] Step (k): KMnO₄, t-BUOH, buffer.

[0101] Reactions for the development of the galactose derivedC-glycoside 138 into protected CA's and diols is illustrate in Scheme23. The common starting material for these synthetic routes (compound138) is disclosed by Petrus, L. et al. (Chem. zvesti. 1982, 36, 103).The reagents and conditions required for the synthesis of compound 209,compound 214, compound 220, and compound 224 are indicated below:

[0102] Step (a):

[0103] (1) 1.1 equivalent DMTCl, DMAP, Pyridine, 12 hour, 20° C.;

[0104] (2) TesOTf, CH₂, 0° C., 1 hour, 83%.

[0105] Step (b):

[0106] (1) LAH, ether, reflux, 2 hour;

[0107] (2)FMOC—Cl, K₂CO₃, THF, H₂O, 0° C., 1 hour, 55%;

[0108] Step (c): 10% HCOOH in CH₂Cl₂, 0° C., 2 minutes, 100%.

[0109] Step (d): RuCl₃, NalO₄, CH₃CN, H₂O, CCl₄, 20° C., 10 minutes,54%.

[0110] Step (e):

[0111] (1) 1 equiv. TsCl, base;

[0112] (2) TESOTf.

[0113] Step (f): NaN₃.

[0114] Step (g): oxidative NEF.

[0115] Step (h): Pd—C, H₂.

[0116] Step (i): FMOC—Cl, base.

[0117] Step (j):

[0118] (1) 1 equiv. PivCl, base;

[0119] (2) TESOTf.

[0120] Step (k):

[0121] (1) oxidative Nef;

[0122] (2) CH₂N₂.

[0123] Step (l): DIBAL—H.

[0124] Step (m): DMTCl, DMAP, Pyridine.

[0125] Step (n): LAH

[0126] Step (o): Nef reaction

[0127] Step (p): LAH.

[0128] An exemplary protocol for synthesizing a hexamer carbopeptoid(CPD 234) starting from galactose derived CA 214, glucosamine derived CA62, and glucose derived CA, using standard methods for solid phasepeptide synthesis is illustrated in Scheme 24. The reagents andcondition for these reactions are as follows:

[0129] Step 1: DCC, HOBT, Et₃, DMF;

[0130] Step 2: Piperidine, DMF

SYNTHETIC METHODS

[0131] Preparation of 37

[0132] To a solution of β-D-Glucose pentaacetate 36 i n nitromethanefrom Aldrich company (0.13 Molar), is added trimethylsilyl cyanide (3.0equivalents) and then SnCl₄ (0.02 equivalents). The mixture is stirredfor one hour and then an aqueous solution of sodium acetate was added tohydrolyze the remaining trimethylsilyl cyanide. The mixture isevaporated and the remaining oil is resuspended in dichloromethane andwashed with sodium acetate solution (1×), water (1×). brine (1×) andthen dried over magnesium sulphate and concentrated. The crude solid isthen recrystallized from methanol to yield 37 as a white solid (47%).scheme 3 step 1; scheme 9, step a.

[0133] Preparation of 38

[0134] The crude product 37 is next dissolved in ethanol (0.15 M) andthen concentrated H₂SO₄ (0.01 equivalents-catalytic) is added. Thereaction mixture is heated to 85° C. for eight hours. The solution isnext concentrated in vacuo and purification by flash columnchromatography affords compound 38. scheme 3 step 2

[0135] Preparation of 39

[0136] To a solution of 38 (1.0 equivalents) in pyridine (.10 Molar), isadded trimethylacetyl chloride (pivaloyl chloride) (2.5 equivalents) at0° C. The reaction is stirred for 2 hours and then diluted withdiethylether and washed with ammonium chloride (2×), copper sulfate(2×), brine (1×), dried over MgSO₄ and concentrated. Purification byflash column chromatography affords compound 39. scheme 3 step 1

[0137] Preparation of 40

[0138] To a solution of 39 (1.0 equivalents) in methylene chloride (0.10Molar), is added diisopropylethylamine (3.3 equivalents) at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 40. scheme 3 step 2

[0139] Preparation of 41

[0140] To a solution of 40 in ethanol (0.13 Molar), is added sodiumethoxide (0.3 equivalents) and the reaction mixture is stirred for twohours at room temperature. The solution is then concentrated in vacuoand purification by flash column chromatography affords compound 41.scheme 3 step 1

[0141] Preparation of 42

[0142] A solution of 41 (1.0 equivalents) in tetrahydrofuran (0.18 M) istreated with DPPA (diphenylphosphorylazide, 2.0 equivalents),triphenylphosphine (1.3 equivalents) and DIAD(diisopropyl-azo-dicarboxylate, 1.3 equivalents). The reaction is heatedto 80° C. for 3 hours and then diluted with ether (2×) and washed with0.5 M aqueous NaOH (2×). The organic layer is dried over MgSO₄ andevaporated. Purification by flash column chromatography affords compound42. scheme 3 step 2

[0143] Preparation of 44

[0144] A solution of 42 (1.0 equivalents) is dissolved in ethanol (0.01M total) at 25° C. The mixture is next exposed to 10% Pd/C (0.1equivalents) and is then subsequently capped with a hydrogen balloon at1 atmosphere. The reaction is stirred for 72 hours and is then filteredthrough celite. The crude mixture is subsequently diluted with ether andwashed with NaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 44. scheme3 step 1

[0145] Preparation of 45

[0146] A solution of 44 (1.0 equivalents) is dissolved in p-dioxanes(0.1 M) and then exposed to a solution 3.0 Molar solution of sodiumhydroxide (1.5 equivalents). The reaction is then stirred for 2 hours at50° C. and is subsequently diluted with ether and washed with a solutionof NH₄Cl (3×), brine (1×) and dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 45. scheme3 step 1

[0147] Preparation of 46

[0148] To a solution of 45 (1.0 equivalents) in methylene chloride (0.10Molar), is added sodium bicarbonate (2.0 equivalents) at 0° C.Subsequent addition of 9-fluorenylmethyl chloroformate (FMOC—Cl, 1.2equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×).brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 46. scheme 3 step 2

[0149] Preparation of 48

[0150] Procedure as described in Methods in Carbohydrate chemistry,Whistler, R., II, 1963, p. 327. A mixture of 80 g anhydrousD-glucosamine hydrochloride or D-galactosamine hydrochloride fromAldrich chemical company, in 200 mL. methanol and 20 g Dowex 50 (H+)acidic resin, is stirred at the boiling point in a round bottom flask.After 24-hr. reaction time, the resin is removed by filtration and ishedthree times with 20 ml. of methanol. The filrate and ishings arecombined and concentrated to about 125 ml by rotovap. The concentrate isallowed to cool to room temperature and the product crystallizesovernight.

[0151] To a solution of free amine, in chloroform (0.5 M), is addedphthalic anhydride (1.5 equiv.) and the reaction mixture is allowed toreflux at 70° C. for 4 h. The product is then crystallized and carriedonto the next step.

[0152] To a solution of triol in methylene chloride (0.5 M), is addedacetic anhydride (3.5 equiv.) and triethyl amine (3.5 equiv.) and thereaction mixture is allowed to stir at 0° C. for 4 h. The product 48, isthen crystallized or purified by flash column chromatography and carriedonto the next step.

[0153] Preparation of 50

[0154] To a solution of N-phthalamido-D-Glucosamine tetraacetae 48 innitromethane (0.13 Molar), is added trimethylsilyl cyanide (3.0equivalents) and then SnCl₄ (0.02 equivalents). The mixture is stirredfor one hour and then an aqueous solution of sodium acetate was added tohydrolyze the remaining trimethylsilyl cyanide. The mixture isevaporated and the remaining oil is resuspended in dichloromethane andwashed with sodium acetate solution (1×), water (1×), brine (1×) andthen dried over magnesium sulphate and concentrated. The crude solid isthen recrystallized from methanol to yield 50 as a white solid (47%).scheme 4

[0155] Preparation of 52

[0156] The crude product 50 is next dissolved in ethanol (0.15 M) andthen concentrated H₂SO₄ (0.01 equivalents-catalytic) is added. Thereaction mixture is heated to 85° C. for eight hours. The solution isnext concentrated in vacuo and purification by flash columnchromatography affords compound 52. scheme 4

Preparation of 54

[0157]

[0158] A solution of 52 (1.0 equivalents) is dissolved in methanol (0.1M total). The reaction is then charged with acetic anhydride (1.1equivalents) and is subsequently stirred for 2 hours at 30° C. Thereaction is next diluted with ether and washed with NaHCO₃ (3×), brine(1×) and dried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 54. scheme 4

[0159] Preparation of 55

[0160] To a solution of 54 (1.0 equivalents) in pyridine (0.10 Molar),is added trimethylacetylchloride (pivaloyl chloride) (2.5 equivalents)at 0° C. The reaction is stirred for 2 hours and then diluted withdiethylether and washed with ammonium chloride (2×), copper sulfate(2×), brine (1×), dried over MgSO₄ and concentrated. Purification byflash column chromatography affords compound 55. scheme 4

[0161] Preparation of 56

[0162] To a solution of 55 (1.0 equivalents) in methylene chloride (0.10Molar). is added diisopropylethylamine (2.2 equivalents) at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (2.2equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×).brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 56. scheme 4

[0163] Preparation of 57

[0164] To a solution of 56 in ethanol (0.13 Molar), is added sodiumethoxide (0.3 equivalents) and the reaction mixture is stirred for twohours at room temperature. The solution is then concentrated in vacuoand purification by flash column chromatography affords compound 57.scheme 4

[0165] Preparation of 58

[0166] A solution of 57 (1.0 equivalents) in tetrahydrofuran (0.18 M) istreated with DPPA (diphenylphosphorylazide, 2.0 equivalents),triphenylphosphine (1.3 equivalents) and DIAD(diisopropyl-azo-dicarboxylate, 1.3 equivalents). The reaction is heatedto 80° C. for 3 hours and then diluted with ether (2×) and washed with0.5 M aqueous NaOH (2×). The organic layer is dried over MgSO₄ andevaporated. Purification by flash column chromatography affords compound58. scheme 4

[0167] Preparation of 60

[0168] A solution of 58 (1.0 equivalents) is dissolved in ethanol (0.01M total) at 25° C. The mixture is next exposed to 10% Pd/C (0.1equivalents) and is then subsequently capped with a hydrogen balloon at1 atm. The reaction is stirred for 72 hours and is then filtered throughcelite. The crude mixture is subsequently diluted with ether and washedwith NaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 60. scheme4

[0169] Preparation of 61

[0170] A solution of 60 (1.0 equivalents) is dissolved in p-dioxanes(0.1 M) and then exposed to a solution 3.0 Molar solution of sodiumhydroxide (1.5 equivalents). The reaction is then stirred for 2 hours at50° C. and is subsequently diluted with ether and washed with a solutionof NH₄Cl (3×), brine (1×) and dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 61. scheme4

[0171] Preparation of 62

[0172] To a solution of 61 (1.0 equivalents) in methylene chloride (0.10Molar), is added sodium bicarbonate (2.0 equivalents) at 0° C.Subsequent addition of 9-fluorenylmethyl chloroformate (FMOC—Cl, 1.2equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 62. scheme 4

[0173] Preparation of 63

[0174] To a stirred solution of the acid 46 (1.0 equivalents) and theamine 60 (1.1 equivalents) in dimethylformamide (0.10 Molar) at )5° C.is added 1-hydroxybenzotriazole (HOBT: 1.1 equivalents). Nextdicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction isstirred for 14 hours. The mixture is diluted with ether. filtered andthe filtrate is washed with aqueous NaHCO₃ (2×). water (2×). and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 63. scheme5 step 1

[0175] Preparation of 64

[0176] To a stirred solution of 63 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added piperidine (1.1equivalents). The reaction is stirred for 1 hour and is then dilutedwith ether, and washed with aqueous CuSO₄ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 64. scheme5 step 2

[0177] Preparation of 65

[0178] To a stirred solution of the acid 62 (1.0 equivalents) and theamine 64 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25° C.,is added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerousiterations can be performed using the acid 62 or intermixing with otheracids including for example acid 46 to form successive oligomers wheren=2 to infinity (a hexamer is shown in scheme 5) to obtain largecarbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents)is added and the reaction is stirred for 14 hours. The mixture isdiluted with ether, filtered and the filtrate is washed with aqueousNaHCO₃ (2×), water (2×), and brine (2×). The organic phase is dried overMgSO4 and then concentrated. Purification by flash column chromatographyaffords compound 65. scheme 5 step 1

[0179] Preparation of 66

[0180] To a stirred solution of 65 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added piperidine (1.1equivalents). The reaction is stirred for 1 hour and is then dilutedwith ether, and washed with aqueous CuSO₄ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 66. Note:numerous iterations can be performed using variable length oligomers of66 to form peptoid oligomers where n=2 to infinity (a hexamer is shownin scheme 5). scheme 5 step 2

[0181] Preparation of 67

[0182] To a stirred solution of the acid 46 (1.0 equivalents) and theamine 66 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25° C,is added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerousiterations can be performed using the acid 46 or intermixing with otheracids including for example acid 62, to form successive oligomers wheren=2 to infinity (a hexamer is shown in scheme 5) to obtain largecarbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents)is added and the reaction is stirred for 14 hours. The mixture isdiluted with ether, filtered and the filtrate is washed with aqueousNaHCO₃ (2×), water (2×), and brine (2×). The organic phase is dried overMgSO₄ and then concentrated. Purification by flash column chromatographyaffords compound 67. scheme 5 step 1

[0183] Preparation of 68

[0184] To a stirred solution of 67 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added piperidine (1.1equivalents). The reaction is stirred for 1 hour and is then dilutedwith ether, and washed with aqueous CuSO₄ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 68. Note:numerous iterations can be performed using variable length oligomers of68 to form peptoid oligomers where n=2 to infinity (a hexamer is shownin scheme 5). scheme 5 step 2

[0185] Preparation of 69

[0186] To a stirred solution of the acid 62 (1.0 equivalents) and theamine 68 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25° C.,is added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerousiterations can be performed using the acid 62, or intermixing with otheracids including for example acid 46, to form successive oligomers wheren=2 to infinity (a hexamer is shown in scheme 5) to obtain largecarbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents)is added and the reaction is stirred for 14 hours. The mixture isdiluted with ether, filtered and the filtrate is washed with aqueousNaHCO₃ (2×), water (2×), and brine (2×). The organic phase is dried overMgSO₄ and then concentrated. Purification by flash column chromatographyaffords compound 69. scheme 5 step 1

[0187] Preparation of 70

[0188] To a stirred solution of 69 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added piperidine (1.1equivalents). The reaction is stirred for 1 hour and is then dilutedwith ether, and washed with aqueous CuSO₄ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 70. Note:numerous iterations can be performed using variable length oligomers of70 to form peptoid oligomers where n=2 to infinity (a hexamer is shownin scheme 5). scheme 5 step 2

[0189] Preparation of 71

[0190] To a stirred solution of the acid 46 (1.0 equivalents) and theamine 70 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25° C,is added 1-hydroxybenzotriazole (HOBT: 1.1 equivalents). Note: numerousiterations can be performed using the acid 46 or intermixing with otheracids including for example acid 62, to form successive oligomers wheren=2 to infinity (a hexamer is shown in scheme 5) to obtain largecarbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents)is added and the reaction is stirred for 14 hours. The mixture isdiluted with ether, filtered and the filtrate is washed with aqueousNaHCO₃ (2×), water (2×), and brine (2×). The organic phase is dried overMgSO₄ and then concentrated. Purification by flash column chromatographyaffords compound 71. scheme 5 step 1

[0191] Preparation of 72

[0192] To a stirred solution of 71 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C, is added piperidine (1.1equivalents). The reaction is stirred for 1 hour and is then dilutedwith ether, and washed with aqueous CuSO₄ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography affords compound 72. Note:numerous iterations can be performed using variable length oligomers of72 to form peptoid oligomers where n=2 to infinity (a hexamer is shownin scheme 5). scheme 5 step 2

[0193] Preparation of 74

[0194] To a stirred solution of 72 (1.0 equivalents) in acetonitrile(0.50 Molar) is added an HF pyridine solution (0.50 M) from Aldrichchemical company. The reaction is allowed to stir for five hours and isthen condensed. The crude 73 oligomer is then resuspended in p-dioxane(0.50 Molar) to which is added a 3.0 Molar solution of NaOH (3.0equivalents). The reaction is stirred for 1 hour at 50° C. and is thenquenched with aqueous NH₄Cl (2×) and subsequently lyophilized.Purification by HPLC chromatography affords compound 74. scheme 5

[0195] Preparation of 76

[0196] To a solution of P-D-Glucose pentaacetate 36 i n nitromethanefrom Aldrich company (0.13 Molar), is added trimethylsilylcyanide (3.0equivalents) and then tin tetrachloride (0.02 equivalents). Note: otherpyranose sugars such as β-D-Mannose, β-D-Galactose pentaacetate andother lewis acids such as BF₃OEt₂ may, be used for alternativederivatives. The mixture is stirred for one hour and then an aqueoussolution of sodium acetate was added to hydrolyze the remainingtrimethylsilylcyanide. The mixture is evaporated and the remaining oilis resuspended in dichloromethane and washed with sodium acetatesolution (1×), water (1×), brine (1×) and then dried over magnesiumsulphate and concentrated. The crude product is next dissolved inethanol (or methanol if the O-methyl glycoside is desired as in scheme20), (0.15 M) and then concentrated H₂SO₄ (0.01 equivalents) is added.The reaction mixture is heated to 85° C. for eight hours. The solutionis next concentrated in vacuo and purification by flash columnchromatography affords compound 76. scheme 6; 76, scheme 20 (as theO-methyl glycoside).

[0197] Preparation of 78

[0198] To Tetrol 76 (1.0 equivalents) in pyridine (0.10 Molar), is addeddimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0° C. Thereaction is stirred for 2 hours and then diluted with diethylether andwashed with ammonium chloride (2×), copper sulfate (2×), brine (1×),dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (4.4 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (4.4equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 78, scheme 6; 78, scheme 20(as the O-methyl glycoside).

[0199] Preparation of 80

[0200] To a solution of 78 (1.0 equivalents) in methylene chloride (0.10Molar) is added a 1.0 M solution of DIBALH in methylene chloride fromAldrich chemical company (1.2 equivalents) at 0° C. Subsequent stirringfor 2 hours is followed by dilution with diethylether and washing withsodium-potassium tartrate (2×), brine (1×) and then MgSO_(4.) Thesolution is then concentrated and purification by flash columnchromatography affords compound 80. scheme 6

[0201] Preparation of 82

[0202] To a solution of 80 (1.0 equivalents) in methylene chloride (0.10M), is added diisopropylethylamine (4.0 equivalents) at 25° C. Thereaction is stirred for 5 minutes and then2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) isadded, as prepared from the procedures of Sinha et al. Nucl. Acids Res.1984, 12, 4539. After 15 minutes the reaction is complete and is nextdiluted with ether and next washed with brine (1×) and is then dried(MgSO₄) and concentrated. Purification by flash column chromatography(silica, 30% ethyl acetate in petroleum ether) affords compound 82 (66%yield). scheme 6

[0203] Preparation of 84

[0204] To 80 (1.0 equivalents) in methylene chloride (0.10 Molar) at 0°C., is added diisopropylethylamine (1.1 equivalents). Subsequentaddition of triethylsilyl trifluoromethanesulfonate (1.1 equivalents) isfollowed by stirring for 2 hours and then the reaction is diluted withdiethylether and washed with ammonium chloride (2×), brine (1×) and thendried (MgSO₄) and concentrated. The crude is then resuspended innitromethane and exposed to 10% Cl₃COOH (1.1 equivalents) in THF (0.10Molar). The reaction is stirred at 0° C. for 2 hours and is then dilutedwith ether and washed with sodium bicarbonate (2×). brine (1×) and thendried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 84. scheme 6

[0205] Preparation of 86

[0206] To a solution of N-phthalamido-D-Glucosamine tetraacetate 48 innitromethane (0.13 Molar), is added trimethylsilyl cyanide (3.0equivalents) and then SnCl₄ (0.02 equivalents). The mixture is stirredfor one hour and then an aqueous solution of sodium acetate was added tohydrolyze the remaining trimethylsilyl cyanide. The mixture isevaporated and the remaining oil is resuspended in dichloromethane andwashed with sodium acetate solution (1×). water (1×), brine (1×) andthen dried over magnesium sulphate and concentrated. The crude productis next dissolved in ethanol (0.15 M) and then concentrated H₂SO₄ (0.04equivalents) is added. The reaction mixture is heated to 85° C. foreight hours. The solution is next concentrated in vacuo and is thenresuspended in methanol (0.10 M) and acetic anhydride (1.1 equivalents)from Aldrich company is added in one step. After 2 hours. condensationand purification by flash column chromatography affords compound 86.scheme 7

[0207] Preparation of 88

[0208] To Triol 86 (1.0 equivalents) in pyridine (0.10 Molar), is addeddimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0° C. Thereaction is stirred for 2 hours and then diluted with diethylether andwashed with ammonium chloride (2×), copper sulfate (2×), brine (1×),dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (3.3 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 88. scheme 7

[0209] Preparation of 90

[0210] To a solution of 88 (1.0 equivalents) in methylene chloride (0.10Molar) is added a 1.0 M solution of DIBALH in methylene chloride fromAldrich chemical company (1.2 equivalents) at 0° C. Subsequent stirringfor 2 hours is followed by dilution with diethylether and washing withsodium-potassium tartrate (2×), brine (1×) and then MgSO_(4.) Thesolution is then concentrated and purification by flash columnchromatography affords compound 90. scheme 7

[0211] Preparation of 92

[0212] To a solution of 90 (1.0 equivalents) in methylene chloride (0.10M). is added diisopropylethylamine (4.0 equivalents) at 25° C. Thereaction is stirred for 5 minutes and then2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) isadded, as prepared from the procedures of Sinha et al. Nucl. Acids Res.1984, 12, 4539. After 15 minutes the reaction is complete and is nextdiluted with ether and next washed with brine (1×) and is then dried(MgSO₄) and concentrated. Purification by flash column chromatography(silica, 30% ethyl acetate in petroleum ether) affords compound 92 (66%yield). scheme 7

[0213] Preparation of 94

[0214] To 90 (1.0 equivalents) in methylene chloride (0.10 Molar) at 0°C., is added diisopropylethylamine (1.1 equivalents). Subsequentaddition of triethylsilyl trifluoromethanesulfonate (1.1 equivalents) isfollowed by stirring for 2 hours and then the reaction is diluted withdiethylether and washed with ammonium chloride (2×), brine (1×) and thendried (MgSO₄) and concentrated. The crude is then resuspended innitromethane and exposed to 10% Cl₃COOH (1.1 equivalents) in THF (0.10Molar). The reaction is stirred at 0° C. for 2 hours and is then dilutedwith ether and washed with sodium bicarbonate (2×), brine (1×) and thendried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 94. scheme 7

[0215] Preparation of 98 (homodimer scheme 8)

[0216] To a solution of 94 (1.0 equivalents) in methylene chloride (0.10M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents) at25° C. Next, a solution of 82 (3.0 equivalents) in methylene chloride(1.0 M), is added dropwise with stirring at 25° C. After 25 minutes, themixture is cooled to 0° C. and I₂ (4.0 equivalents), 2,6 lutidine (4.0equivalents) in THF (1.0 M) is added to oxidize the phosphoamidate tothe phosphate (Alternatively m-chloroperoxybenzoic acid (4.5equivalents) is added). The reaction is next stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is suspended in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 98 (scheme 8).

[0217] Preparation of 102 (heterotrimer scheme 8)

[0218] To a solution of 98 (1.0 equivalents) in methylene chloride (0.10M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents) at25° C. Next, a solution of 92 (3.0 equivalents) in methylene chloride(1.0 M), is added dropwise with stirring at 25° C. After 25 minutes, themixture is cooled to 0° C. and I₂ (4.0 equivalents), 2,6 lutidine (4.0equivalents) in THF (1.0 M) is added to oxidize the phosphoamidate tothe phosphate (Alternatively m-chloroperoxybenzoic acid (4.5equivalents) is added). The reaction is next stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is suspended in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 102 (scheme 8).

[0219] Preparation of 106 (heterotetramer scheme 8)

[0220] To a solution of 102 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 82 (3.0 equivalents) in methylene chloride(1.0 M), is added dropwise with stirring at 25° C. After 25 minutes, themixture is cooled to 0° C. and I₂ (4.0 equivalents), 2,6 lutidine (4.0equivalents) in THF (1.0 M) is added to oxidize the phosphoamidate tothe phosphate (Alternatively m-chloroperoxybenzoic acid (4.5equivalents) is added). The reaction is next stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is suspended in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 106 (scheme 8).

[0221] Preparation of 110 (heteropentamer scheme 8)

[0222] To a solution of 106 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 92 (3.0 equivalents) in methylene chloride(1.0 M), is added dropwise with stirring at 25° C. After 25 minutes. themixture is cooled to 0° C. and I₂ (4.0 equivalents), 2.6 lutidine (4.0equivalents) in THF (1.0 M) is added to oxidize the phosphoamidate tothe phosphate (Alternatively m-chloroperoxybenzoic acid (4.5equivalents) is added). The reaction is next stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is suspended in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 110 (scheme 8).

[0223] Preparation of 114 (heterohexamer scheme 8)

[0224] To a solution of 110 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 82 (3.0 equivalents) in methylene chloride(1.0 M), is added dropwise with stirring at 25° C. After 25 minutes, themixture is cooled to 0° C. and I₂ (4.0 equivalents), 2,6 lutidine (4.0equivalents) in THF (1.0 M) is added to oxidize the phosphoamidate tothe phosphate (Alternatively m-chloroperoxybenzoic acid (4.5equivalents) is added). The reaction is next stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is suspended in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 114 (scheme 8).

[0225] Preparation of 116 (heterohexamer scheme 8)

[0226] To a solution of 114 (1.0 equivalents) in methylene chloride(0.10 M), is added a solution of HF-pyridine (1.0 M) at 0° C. Thereaction is next stirred for an additional 30 minutes and is nextdiluted with ether and washed with a saturated solution of sodiumbicarbonate (3×). copper sulfate solution to remove the pyridine (2×)brine (1×), dried (MgSO₄) and concentrated. Purification by flash columnchromatography and then the product is resuspended in concentratedaqueous ammonium hydroxide and acetonitrile (1:1), (0.1 M total). Thereaction is then stirred for 2 hours at 50° C and is subsequentlydiluted with ether and washed with NaHCO₃ (3×), brine (1×) and dried(MgSO₄) and concentrated. Purification by flash column chromatographyaffords compound 116 scheme 8.

[0227] Preparation of 125

[0228] To a solution of β-D-Glucose pentaacetate in nitromethane fromAldrich company (0.13 Molar), is added trimethylsilylcyanide (3.0equivalents) and then borontrifluoride etherate (0.02 equivalents).Note: other pyranose sugars such as β-D-Mannose, β-D-Galactosepentaacetate and other lewis acids such as SnCl_(4,) may be used foralternative derivatives. The mixture is stirred for one hour and then anaqueous solution of sodium acetate was added to hydrolyze the remainingtrimethylsilylcyanide. The mixture is evaporated and the remaining oilis resuspended in dichloromethane and washed with sodium acetatesolution (1×). water (1×), brine (1×) and then dried over magnesiumsulphate and concentrated. The crude solid is then recrystallized frommethanol to yield 125 (also 37) as a white solid (47%). scheme 9 step a

[0229] Preparation of 126

[0230] To a solution of 125 in methanol (0.13 Molar), is added sodiummethoxide (0.3 equivalents) and the reaction mixture is stirred for twohours at room temperature. The dark brown solution is then concentratedin vacuo to give a dark brown syrup of compound 126 which is carried onwithout purification as a crude oil for the next step. scheme 9 step b

[0231] Preparation of 127

[0232] The crude product 126 is dissolved in 25% NaOH (0.5 M) and heatedat reflux for 18 hours (vigorous reflux is necessary). Next, thesolution is diluted with an addition of water (0.1 M) and to thissolution is added Amberlite 112120 resin (H⁺-form) and is then stirred.The supernatant is then decanted and the resin is washed until theeluate is colorless. The eluate is then collected, condensed andazeotroped with MeOH which yields 127 as a crude, pale yellow syrup(47%).

[0233] Preparation of 130

[0234] The crude product 127 is next dissolved in methanol (0.15 M) andthen concentrated HCl (0.01 equivalents) is added. The reaction mixtureis heated to 85° C. for eight hours. The solution is next concentratedin vacuo and purification by flash column chromatography (silica, 20%methanol in ethyl acetate), affords compound 130 as a white solid (60%yield). scheme 9 step d

[0235] Preparation of 131

[0236] To a solution of 130 (1.0 equivalents) in dimethylformamide (0.23Molar), is added imidazole (2.5 equivalents) at 0° C. Subsequentaddition of tert-Butyl-diethylsilyichloride (2.5 equivalents) isfollowed by stirring for 2 hours and then the reaction is diluted withdiethylether and washed with ammonium chloride (2×), brine (1×) and thendried (MgSO₄) and concentrated. Purification by flash columnchromatography (silica, 50% ethyl acetate) affords compound 131 as awhite solid (93% yield). scheme 9 step e Note: the molecule can beprotected with other primary directing protecting groups such as DMT(dimethoxytrityl), and TBDPS tert-butvldiphenlysilyl, etc.

[0237] Preparation of 132

[0238] To a solution of 131 (1.0 equivalents) in dimethylformamide (0.23M), is added Ag₂O (6.0 equivalents) at 25° C. Benzyl bromide (9.0equivalents) is next added and the reaction is allowed to stir for 20hours. The reaction is diluted with diethylether and washed withammonium chloride (2×), brine (1×) and then dried (MgSO₄) andconcentrated. Purification by flash column chromatography (silica, 20%ethyl acetate) affords compound 132 (83% yield). scheme 9 step f Note:the choice of the protecting group is relative and the molecule can beprotected with other protecting groups at C2, C3, C4, such as PMB(paramethoxvbenzyl), TES (triethvlsilyl), TBS (tertbutvldimethvlsilyl),etc.

[0239] Preparation of 134

[0240] To a solution of 132 (1.0 equivalents) in tetrahydrofuran (0.08M), is added diisobutvlaluminumhydride (DIBALH) (3.0 equivalents) at 0°C. The reaction is stirred for 1 hour and then quenched with methanoland diluted with ether. The reaction is next worked-up with ammoniumchloride (2×), brine (1×) and is then dried (MgSO₄) and concentrated.Purification by flash column chromatography (silica. 20% ethyl acetate)affords compound 134 (66% yield). scheme 9 step g

[0241] Preparation of 136

[0242] To a solution of 134 (1.0 equivalents) in pyridine (10.0equivalents), is added naphthoyl chloride (3.0 equivalents) from Aldrichcompany (3.0 equivalents) at 25° C. The reaction is stirred for 45minutes and then diluted with ether and worked-up with a saturatedsolution of CuSO₄ (2×), brine (1×) and is then dried (MgSO₄) andconcentrated. The crude product is then exposed to aceticacid/tetrahydrofuran/water (3:1:1) at 25° C. and allowed to stir for 15hours. The reaction is then diluted with ether and worked-up with brine(2×) and is then dried (MgSO₄) and concentrated. Purification by flashcolumn chromatography (silica. 20% ethyl acetate) affords compound 136(95% yield). Note: alternatively, one could originally protect the C7position as a DMT (dimethoxytrityl) functionality) and protect the C1position as a TES (triethyl silyl) group. Subsequent mild acidhydrolysis of the DMT group leads to the above compound with the TESgroup at the C1 position and a free hydroxyl at the C7 position. scheme9 step h

[0243] Preparation of 138

[0244] To a solution of 134 (1.0 equivalents) in methylene chloride(0.10 M), is added diisopropylethylamine (4.0 equivalents) at 25 ° C.The reaction is stirred for 5 minutes and then2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) isadded, as prepared from the procedures of Sinha et al. Nucl. Acids Res.1984, 12, 4539. After 15 minutes the reaction is complete and is nextdiluted with ether and next washed with brine (1×) and is then dried(MgSO₄) and concentrated. Purification by flash column chromatography(silica, 30% ethyl acetate in petroleum ether) affords compound 138 (66%yield). scheme 9 step i

[0245] It should be noted that the oligomerization process as shownbelow in scheme 9, uses the same C-glycoside 138 in an iterativefashion. The process can be extended however to include a pool of randomor ordered C-glycosides as depicted in scheme 8.

[0246] Preparation of 140

[0247] To a solution of 136 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 138 (3.0 equivalents) in methylenechloride (1.0 M), is added dropwise with stirring at 25° C. After 25minutes, the mixture is cooled to 0° C. and m-chloroperoxybenzoic acid(4.5 equivalents) is added. The reaction is stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography (silica, 50% ethyl acetate in petroleum ether) affordscompound 140 (97% yield). scheme 9 step j Note the process can iterateas many times as possible to build large carbonucleotide libraries.

[0248] Preparation of 142

[0249] A solution of 140 (1.0 equivalents) in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M) is stirred for 18 hours at25° C. The reaction is then diluted with ether and washed with NaHCO₃(3×), brine (1×) and dried (MgSO₄) and concentrated. Purification byflash column chromatography (silica, 60% ethyl acetate in petroleumether) affords compound 142 (95% yield). scheme 9 step k Note theprocess can iterate as manya times as possible to build largecarbonucleotide libraries.

[0250] Preparation of 144

[0251] To a solution of 138 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 142 (3.0 equivalents) in methylenechloride (1.0 M), is added dropwise with stirring at 25° C. After 25minutes, the mixture is cooled to 0° C. and m-chloroperoxybenzoic acid(4.5 equivalents) is added. The reaction is stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography (silica, 50% ethyl acetate in petroleum ether) affordscompound 144 (97% yield). scheme 9 step j Note the process can iterateas manya times as possible to build large carbonucleotide libraries.

[0252] Preparation of 146

[0253] A solution of 144 (1.0 equivalents) in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M total) is stirred for 18hours at 25° C. The reaction is then diluted with ether and washed withNaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated. Purificationby flash column chromatography (silica, 60% ethyl acetate in petroleumether) affords compound 146 (95% yield). scheme 9 step k Note theprocess can iterate as many times as possible to build largecarboniucleotide libraries.

[0254] Preparation of 148

[0255] To a solution of 138 (1.0 equivalents) in methylene chloride(0.10 M), is added 1-H-tetrazole from Aldrich company (10.0 equivalents)at 25° C. Next, a solution of 146 (3.0 equivalents) in methylenechloride (1.0 M), is added dropwise with stirring at 25° C. After 25minutes, the mixture is cooled to 0° C. and m-chloroperoxybenzoic acid(4.5 equivalents) is added. The reaction is stirred for an additional 5minutes and is next diluted with ether and washed with brine (1×) anddried (MgSO₄) and concentrated. Purification by flash columnchromatography (silica. 50% ethyl acetate in petroleum ether) affordscompound 148 (97% yield). scheme 9 step j Note the process can iterateas man), times as possible to build large carbontucleotide libraries.

[0256] Preparation of 150

[0257] A solution of 148 (1.0 equivalents) in aceticacid-tetrahydrofuran-water (3:1:1), (0.01 M total) is stirred for 18hours at 25° C. The reaction is then diluted with ether and washed withNaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated. Purificationby flash column chromatography (silica, 60% ethyl acetate in petroleumether) affords compound 150 (95% yield). scheme 9 step k Note theprocess can iterate as many times as possible to build largecarbonucleotide libraries.

[0258] Preparation of 152

[0259] A solution of 150 (1.0 equivalents) is dissolved in concentratedaqueous ammonium hydroxide and acetonitrile (1:1), (0.1 M total). Thereaction is then stirred for 2 hours at 50° C. and is subsequentlydiluted with ether and washed with NaHCO₃ (3×). brine (1×) and dried(MgSO₄) and concentrated. Purification by flash column chromatography(silica. 80% ethyl acetate in petroleum ether) affords compound 152 (88%yield). scheme 9 step L

[0260] Preparation of 154

[0261] A solution of 152 (1.0 equivalents) is dissolved in a mixture ofethanol-tetrahydrofuran-acetic acid (2:1:1), (0.01 M total) at 25° C.The mixture is next exposed to 10% Pd/C (1.0 equivalents) and is thensubsequently capped with a hydrogen balloon at 1 atmosphere. Thereaction is stirred for 72 hours and is then filtered through celite.The crude mixture is subsequently diluted with ether and washed withNaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated. Purificationby flash column chromatography (silica, 100% ethyl acetate in petroleumether) affords compound 154 (78% yield). scheme 9 step m

[0262] Preparation of 174 (R group=OTES, NPhth or NHAc)

[0263] To a solution of tetraacetate derived from 36 or 48 (glucose orglucosamine derived) in methylene chloride (0.1 molar) is added a 1.0molar solution of Co₂(CO)₈ (1.5 equivalents ) in methylene chloride anddiethylmethylsilane (1.5 equivalents) at 0° C. To the stirring reactionmixture, a stream of carbon monoxide is bubbled at 1 ml per 10 secondsfor 30 minutes. The reaction mixture is then quenched with water (1.5equivalents), diluted with ether, washed with sodium bicarbonate (2×),brine (1×) and dried over magnesium sulfate. The crude is purified bycolumn chromatography and affords product 174.

[0264] Preparation of 176 (R group=OTES, NPhth or NHAc)

[0265] To a solution of compound 174 in acetonitrile/water (1:1 ratio,0.1 molar combined), is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)at 25° C. and the muddy black mixture is allowed to stir for 1.5 h. Themixture is then diluted with ether (25 mL), washed with water (2×5.0 mL)and brine (1×5 mL). The aqueous layer is back extracted (2×),recombined, and the organic layer was then dried MgSO₄ and evaporated.Purification by flash column chromatography yields the desired product176.

[0266] Preparation of 178 (R group=OTES, NPhth or NHAc)

[0267] A solution of triacetate 176 (1.0 equiv.) in methanol (0.5 M), istreated with NaOMe (0.4 equiv.) and allowed to stir at 25° C. for 24 h.The reaction mixture is then condensed and purified by flash columnchromatography to afford compound 178.

[0268] Preparation of 180 (R group=OTES, NPhth or NHAc)

[0269] To triol 178 (1.0 equivalents) in pyridine (0.10 Molar), is addeddimethyoxytritylchloride (DMT chloride) (1.5 equivalents) at 0° C. Thereaction is stirred for 2 hours and then diluted with diethylether andwashed with ammonium chloride (2×). copper sulfate (2×). brine (1×),dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (3.3 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×).brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords the intermediate acid, which is thenresuspended in THF (1.0 M) and exposed to a 1.0 M solution of BH₃-THF(1.5 equivalents) at 0° C. for 1 hour. The reaction is then quenchedwith methanol for an additional hour and the crude is then diluted withdiethylether and washed with ammonium chloride (2×), brine (1×) and thendried (MgSO₄) and concentrated. Purification by flash columnchromatography affords the desired tetraprotected alcohol 180.

[0270] Preparation of 181 (R group=OTES, NPhth or NHAC)

[0271] To a solution of 180 (1.0 equivalents) in methylene chloride(0.10 M), is added tetrazole (4.0 equivalents) at 25° C. The reaction isstirred for 5 minutes and then2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv.) isadded, as prepared from the procedures of Sinha et al. Nucl. Acids Res.1984, 12, 4539. After 15 minutes the reaction is complete and is nextdiluted with ether and next washed with brine (1×) and is then dried(MgSO₄) and concentrated. Purification by flash column chromatography(silica. 30% ethyl acetate in petroleum ether) affords compound 181 (66%vield). scheme 21

[0272] Preparation of 182 (R group=OTES. NPhth or NHAc) To a solution oftriol 178 (0.0 equiv.) in CH₂Cl₂ (0.5 M) at 0° C. was addedtriethylamine (1.2 equiv.), 4-DMAP (0.10 equiv.) and then TOSCl (1.1equiv.). The reaction is stirred for 1 h and then is quenched withsaturated ammonium chloride (1.5 mL), diluted with ethyl acetate (25mL), washed with water (2×5 mL). brine (1×5 mL), back-extracted (2×),recombined, dried (MgSO₄) and evaporated. The compound is purified byflash column chromatography and then a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diusopropylethylamine (2.2 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (2.2equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords the protected tosylate/acid 182.

[0273] Preparation of 183 (R group=OTES. NPhth or NHAc)

[0274] To a solution of triol 182 (0.0 equiv.) in CH₂Cl₂ (0.5 M) at 0°C., is added sodium-azide (1.2 equiv.) from Aldrich chemical company at0° C. The reaction is stirred for 1 h and then is quenched withsaturated ammonium chloride (1.5 mL), diluted with ethyl acetate (25mL), washed with water (2×5 mL), brine (1×5 mL), back-extracted (2×).recombined, dried (MgSO₄) and evaporated. The compound is purified byflash column chromatography and affords compound 183.

[0275] Preparation of 185 (R group=OTES, NPhth or NHAc)

[0276] A solution of 183 (1.0 equivalents) in ethanol (0.01 M total) at25° C. is exposed to 10% Pd(OH)₂—C (0.1 equivalents) and is thensubsequently capped with a hydrogen balloon at 1 atmosphere. Thereaction is stirred for 72 hours and is then filtered through celite.The crude mixture is subsequently diluted with ether and washed withNaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated. Purificationby flash column chromatography affords compound 185 scheme 21.

[0277] Preparation of 191

[0278] A solution of starting material 190 as disclosed by Schmidt, R.R. et al. (Liebigs Ann. Chem. 1987, 825), (1.0 equivalents) is dissolvedin a mixture of ethanol-tetrahydrofuran-acetic acid (2:1:1), (0.01 Mtotal) at 25° C. The mixture is next exposed to 10% Pd/C (1.0equivalents) and is then subsequently capped with a hydrogen balloon at1 atmosphere. The reaction is stirred for 72 hours and is then filteredthrough celite. The crude mixture is subsequently diluted with ether andwashed with NaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated.Purification by flash column chromatography (silica, 100% ethyl acetatein petroleum ether) affords compound 191. scheme 22 step a

[0279] Preparation of 192

[0280] To a solution of 191 (1.0 equivalents) in methylene chloride(0.10 Molar) is added tosylchloride (1.2 equivalents) at 0° C.Subsequent addition of triethylamine (1.5 equivalents) is followed bystirring for 2 hours and then the reaction is diluted with diethyletherand washed with ammonium chloride (2×), brine (1×) and then dried(MgSO₄) and concentrated to afford the crude tosylate. Next a solutionof the crude intermediate (1.0 equivalents) is dissolved in methylenechloride (0.10 Molar) and diusopropylethylamine (3.3 equivalents) isadded at 0° C. Subsequent addition of triethvlsilyltrifluoromethanesulfonate (3.3 equivalents) is followed by stirring for2 hours and then the reaction is diluted with diethylether and washedwith ammonium chloride (2×), brine (1×) and then dried (MgSO₄) andconcentrated. Purification by flash column chromatography affordscompound 192. scheme 22 step b

[0281] Preparation of 193

[0282] To a solution of 192 (1.0 equivalents) in methylene chloride(0.10 Molar) is added sodium azide from Aldrich chemical company (1.2equivalents) at 0° C. Subsequent stirring for 2 hours is followed bydilution with diethylether and washing with ammonium chloride (2×),brine (1×) and then MgSO₄. The solution is then concentrated andpurification by flash column chromatography affords compound 193. scheme22 step c

[0283] Preparation of 194

[0284] To solution of 193 in CCl₄ (0.33 M). CH₃CN (0.33 M) and water(0.22 M) at 0° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 1.5 h. The mixture isthen diluted with ether (25 mL), washed with water (2×5.0 mL) and brine(1×5 mL). The aqueous layer is back extracted (2×), recombined, and theorganic layer iss then dried MgSO₄ and evaporated. Purification by flashcolumn chromatography affords the compound 194. scheme 22 step d

[0285] Preparation of 196

[0286] A solution of 194 (1.0 equivalents) is dissolved in ethanol (0.01M total) at 25° C. The mixture is next exposed to 10% Pd/C (0.1equivalents) and is then subsequently capped with a hydrogen balloon at1 atmosphere. The reaction is stirred for 72 hours and is then filteredthrough celite. The crude mixture is subsequently diluted with ether andwashed with NaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated.Next, to a solution of crude amine (1.0 equivalents) in methylenechloride (0.10 Molar), is added sodium bicarbonate (2.0 equivalents) at0° C. Subsequent addition of 9-fluorenvlmethyl chloroformate (FMOC—Cl,1.2 equivalents) is followed by stirring for 2 hours and then thereaction is diluted with diethylether and washed with ammonium chloride(2×), brine (1×) and then dried (MgSO₄) and concentrated. Purificationby flash column chromatography affords compound 196. scheme 22 steps e-f

[0287] Preparation of 197

[0288] To Tetrol 191 (1.0 equivalents) in pyridine (0.10 Molar), isadded dimethyoxytritvlchloride (DMT chloride) (2.5 equivalents) at 0° C.The reaction is stirred for 2 hours and then diluted with diethyletherand washed with ammonium chloride (2×). copper sulfate (2×), brine (1×),dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (3.3 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirrinn for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 197. scheme 22 step g

[0289] Preparation of 198

[0290] To solution of 197 in CCl₄ (0.33 M), CH₃CN (0.33 M) and water(0.22 M) at 0° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 1.5 h. The mixture isthen diluted with ether (25 mL), washed with water (2×5.0 mL) and brine(1×5 mL). The crude is then resuspended in a mixture of methylenechloride/water (1:1, 0.1 M total) and diazomethane (1.2 equivalents) isgradually dropped into the flask via an addition funnel at the rate of 1drop/10 seconds. After complete addition the mixture is diluted withether, washed with brine (2×) and the aqueous laver is back extracted(2×) recombined, and the organic laver is then dried MgSO₄ andevaporated. Purification by flash column chromatography affords thecompound 198. scheme 22 step h

[0291] Preparation of 200

[0292] To a solution of 198 (1.0 equivalents) in methylene chloride(0.10 Molar) is added a 1.0 M solution of DIBALH in methylene chloridefrom Aldrich chemical company (1.2 equivalents) at 0° C. Subsequentstirring for 2 hours is followed by dilution with diethylether andwashing with sodium—potassium potassium tartrate (2×), brine (1×) andthen MgSO_(4.) The solution is then concentrated and purification byflash column chromatography affords compound 200. scheme 22 step i

[0293] Preparation of 201

[0294] A solution of 200 (1.0 equivalents) in tetrahydrofuran (0.18 M)is treated with DPPA (diphenylphosphorylazide, 2.0 equivalents),triphenylphosphine (1.3 equivalents) and DIAD(diisopropyl-azo-dicarboxylate, 1.3 equivalents). The reaction is heatedto 80° C. for 3 hours and then diluted with ether (2×) and washed with0.5 M aqueous NaOH (2×). The organic layer is dried over MgSO₄ andevaporated. Purification by flash column chromatography affords compound201. scheme 22 step j

[0295] Preparation of 202

[0296] A solution of 201 (1.0 equivalents) is dissolved in ethanol (0.01M total) at 25° C. The mixture is next exposed to 10% Pd/C (0.1equivalents) and is then subsequently capped with a hydrogen balloon atI atmosphere. The reaction is stirred for 72 hours and is then filteredthrough celite. The crude mixture is subsequently diluted with ether andwashed with NaHCO₃ (3×), brine (1×) and dried (MgSO₄) and concentrated.Next. to a solution of crude amine (1.0 equivalents) in methylenechloride (0.10 Molar). is added sodium bicarbonate (2.0 equivalents) at0° C. Subsequent addition of 9-fluorenylmethvl chloroformate (FMOC—Cl.1.2 equivalents) is followed by stirring for 2 hours and then thereaction is diluted with diethylether and washed with ammonium chloride(2×), brine (1×) and then dried (MgSO₄) and concentrated. Purificationby flash column chromatography affords compound 202. scheme 22 step e

[0297] Preparation of 204

[0298] To a solution of 202 (1.0 equivalents) in methylene chloride(0.10 Molar) is added 10% HCOOH from Aldrich chemical company (1.2equivalents) at 0° C. Subsequent stirring for 2 hours is followed bydilution with diethylether and washing with sodium bicarbonate (2×),brine (1×) and then MgSO₄. The solution is then resuspended in t-BuOH(0.10 M) and pH 7 buffer (0.10 M) and is then exposed to KMnO₄ (1.2equivalents) for 2 hours at 0° C. The reaction mixture is next washedwith sodium bicarbonate (2×), brine (1×) and then MgSO_(4.) The organiclayer is then concentrated and purified by flash column chromatographyto afford compound 204. scheme 22 step k

[0299] Preparation of 206

[0300] To Tetrol 205 (1.0 equivalents) (as disclosed by Petrus, L. etal.Chem. zvesti. 1982, 36, 103) in pyridine (0.10 Molar), is addeddimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0° C. Thereaction is stirred for 2 hours and then diluted with diethylether andwashed with ammonium chloride (2×) copper sulfate (2×), brine (1×),dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (3.3 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 206. scheme 23 step a

[0301] Preparation of 207

[0302] To a solution of 206 (1.0 equivalents) in diethylether (0.08 M),is added lithiumaluminumhydride (LAH) (1.5 equivalents) at 30° C. Thereaction is refluxed for 2 hours and then quenched with methanol anddiluted with ether. The reaction is next worked-up with sodium potassiumtartrate (2×), brine (1×) and is then dried (MgSO₄ ) and concentrated.The crude mixture is resuspended in mcthylene chloride (0.10 Molar) andto it is added sodium bicarbonate (2.0 equivalents) at 0° C. Subsequentaddition of 9-fluorenvlmethyl chloroformate (FMOC—Cl, 1.2 equivalcnt.s)is followed by stirrin for 2 hours and then the reaction is, dilutedwith diethvlether and washed with ammonium chloride (2×). brine (1×) andthen dried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 207. scheme 23 step b

[0303] Preparation of 208

[0304] To a solution of 207 (1.0 equivalents) in methylene chloride(0.10 Molar) is added10% HCOOH (1.1 equivalents). The reaction isstirred at 0° C. for 2 minutes and is then diluted with ether and washedwith sodium bicarbonate (2×), brine (1×) and then dried (MgSO₄) andconcentrated. Purification by flash column chromatography affordscompound 208. scheme 23 step c

[0305] Preparation of 209

[0306] To solution of 208 in CCl₄ (0.33 M), CH₃CN (0.33 M) and water(0.22 M) at 20° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 10 min. The mixtureis then diluted with ether (25 mL). washed with water (2×5.0 mL) andbrine (1×5 mL). The aqueous layer is back extracted (2×), recombined,and the organic layer iss then dried MgSO₄ and evaporated. Purificationby flash column chromatography affords the compound 209. scheme 23 stepd

[0307] Preparation of 210

[0308] To a solution of 205 (1.0 equivalents) in methylene chloride(0.10 Molar) is added tosylchloride (1.2 equivalents) at 0° C.Subsequent addition of triethylamine (1.5 equivalents) is followed bystirring for 2 hours and then the reaction is diluted with diethyletherand washed with ammonium chloride (2×). brine (1×) and then dried(MgSO₄) and concentrated to afford the crude tosylate. Next a solutionof the crude intermediate (1.0 equivalents) is dissolved in methylenechloride (0.10 Molar) and diusopropylethylamine (3.3 equivalents) isadded at 0° C. Subsequent addition of triethylsilyltrifluoromethanesulfonate (3.3 equivalents) is followed by stirrina for2 hours and then the reaction is diluted with diethylether and washedwith ammonium chloride (2×), brine (1×) and then dried (MgSO₄) andconcentrated. Purification by flash column chromatography affordscompound 210. scheme 23 step e

[0309] Preparation of 211

[0310] To a solution of 210 (1.0 equivalents) in methylene chloride(0.10 Molar) is added sodium azide from Aldrich chemical company (1.2equivalents) at 0° C. Subsequent stirring for 2 hours is followed bydilution with diethylether and washing with ammonium chloride (2×),brine (1×) and then M gSO_(4.) The solution is then concentrated andpurification by flash column chromatography affords compound 211. scheme23 step f

[0311] Preparation of 212

[0312] To solution of 211 in CCl₄ (0.33 M), CH₃CN (0.33 M) and water(0.22 M) at 20° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 10 min. The mixtureis then diluted with ether (25 mL), washed with water (2×5.0 mL) andbrine (1×5 mL). The aqueous layer is back extracted (2×), recombined,and the organic layer iss then dried MgSO₄ and evaporated. Purificationby flash column chromatography affords the compound 212. scheme 23 step

[0313] Preparation of 213

[0314] A solution of 212 (1.0 equivalents) in ethanol (0.01 M total) at25° C. is exposed to 10% Pd/C (0.1 equivalents) and is then subsequentlycapped with a hydrogen balloon at 1 atmosphere. The reaction is stirredfor 72 hours and is then filtered through celite. The crude mixture issubsequently diluted with ether and washed with NaHCO₃ (3×), brine (1×)and dried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 213. scheme 23 step h

[0315] Preparation of 214

[0316] Compound 213 is suspended in methylene chloride (0.10 Molar) andto it is added sodium bicarbonate (2.0 equivalents) at 0° C. Subsequentaddition of 9-fluorenylmethyl chloroformate (FMOC—Cl, 1.2 equivalents)is followed by stirring for 2 hours and then the reaction is dilutedwith diethylether and washed with ammonium chloride (2×), brine (1×) andthen dried (MgSO₄) and concentrated. Purification by flash columnchromatography affords compound 214. scheme 23 step i

[0317] Preparation of 215

[0318] To a solution of 205 (1.0 equivalents) in pyridine (0.10 Molar),is added trimethylacetyl chloride (pivaloyl chloride) (2.5 equivalents)at 0° C. The reaction is stirred for 2 hours and then diluted withdiethylether and washed with ammonium chloride (2×). copper sulfate(2×), brine (1×), dried over MgSO₄ and concentrated. Next a solution ofthe crude intermediate (1.0 equivalents) is dissolved in methylenechloride (0.10 Molar) and diusopropylethylamine (3.3 equivalents) isadded at 0° C. Subsequent addition of triethylsilyltrifluoromethanesulfonate (3.3 equivalents) is followed by stirring for2 hours and then the reaction is diluted with diethylether and washedwith ammonium chloride (2×). brine (1×) and then dried (MgSO₄) andconcentrated. Purification by flash column chromatography affordscompound 215. scheme 23 step j

[0319] Preparation of 216

[0320] To solution of 215 in CCl₄ (0.33 M), CH₃CN (0.33 M) and water(0.22 M) at 20° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 10 min. The mixtureis then diluted with ether (25 mL), washed with water (2×5.0 mL) andbrine (1×5 mL). The aqueous layer is back extracted (2×), recombined.and the organic laver is then dried MgSO₄ and evaporated. The crude isthen resuspended in a mixture of methylene chloride/water (1:1,0.1 Mtotal) and diazomethane (1.2 equivalents) is gradually dropped into theflask via an addition funnel at the rate of 1 drop/10 seconds. Aftercomplete addition the mixture is diluted with ether. washed with brine(2×) and the aqueous layer is back extracted (2×) recombined. and theorganic layer is then dried MgSO₄ and evaporated. Purification by flashcolumn chromatography affords the compound 216. scheme 23 step k

[0321] Preparation of 217

[0322] To a solution of 216 (1.0 equivalents) in methylene chloride(0.10 Molar) is added a 1.0 M solution of DIBALH in methylene chloridefrom Aldrich chemical company (1.2 equivalents) at 0° C. Subsequentstirring for 2 hours is followed by dilution with diethylether andwashing with sodium—potassium tartrate (2×), brine (i×) and then MgSO₄.The solution is then concentrated and purification by flash columnchromatography affords compound 217. scheme 23 step I

[0323] Preparation of 218

[0324] To 217 (1.0 equivalents) in pyridine (0.10 Molar), is addeddimethyoxvtritvlchloride (DMT chloride) (1.1 equivalents) at 0° C. Thereaction is stirred for 2 hours and then diluted with diethylether andwashed with ammonium chloride (2×), copper sulfate (2×), brine (1×),dried over MgSO₄ and concentrated. Purification by flash columnchromatography affords compound 218. scheme 23 step m

[0325] Preparation of 220

[0326] To a solution of 218 (1.0 equivalents) in diethylether (0.08 M),is added lithiumaluminumhydride (LAH) (1.5 equivalents) at 30° C. Thereaction is refluxed for 2 hours and then quenched with methanol anddiluted with ether. The reaction is next worked-up with sodium potassiumtartrate (2×), brine (1×) and is then dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 220. scheme23 step n

[0327] Preparation of 221

[0328] To Tetrol 205 (1.0 equivalents) in pyridine (0.10 Molar), isadded dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0° C.The reaction is stirred for 2 hours and then diluted with diethyletherand washed with ammonium chloride (2×). copper sulfate (2×), brine (1×).dried over MgSO₄ and concentrated. Next a solution of the crudeintermediate (1.0 equivalents) is dissolved in methylene chloride (0.10Molar) and diisopropylethylamine (3.3 equivalents) is added at 0° C.Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×).brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords compound 221. scheme 23 step a

[0329] Preparation of 222

[0330] To solution of 221 in CCl₄ (0.33 M), CH₃CN (0.33 M) and water(0.22 M) at 20° C. is added RuCl₃ (0.03 equiv.) and NaIO₄ (4.0 equiv.)and the muddy black mixture is allowed to stir for 10 min. The mixtureis then diluted with ether (25 mL), washed with water (2×5.0 mL) andbrine (1×5 mL). The aqueous layer is back extracted (2×), recombined,and the organic layer iss then dried MgSO₄ and evaporated. Purificationby flash column chromatography affords the compound 222. scheme 23 stepo.

[0331] Preparation of 224

[0332] To a solution of 222 (1.0 equivalents) in diethvlether (0.08 M),is added lithiumaluminumhydride (LAH) (1.5 equivalents) at 30° C. Thereaction is refluxed for 2 hours and then quenched with methanol anddiluted with ether. The reaction is next worked-up with sodium potassiumtartrate (2×), brine (1×) and is then dried (MgSO₄) and concentrated.Purification by flash column chromatography affords compound 224. scheme23 step p

[0333] Preparation of 216

[0334] To a stirred solution of the acid 214 (1.0 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Nextdicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction isstirred for 1 hour in the presence of an appropriately substituted solidsupport (N-(2-Aminoethyl)-3-amino-propyl glass; aminopolystyrene resin;aminopropyl glass; isothiocyanato glass, all with or without a linkerextending from the amino group on the support etc. from Sigma Company).The mixture is then diluted with ether, filtered and the filtrate iswashed with aqueous NaHCO₃ (2×), water (2×), and brine (2×). The organicphase is dried over MgSO₄ and then concentrated.

[0335] Preparation of 226; 228; 230 or 232

[0336] To a stirred solution of the acid 214; 62; 215 or 62 ( 1.0equivalents) and the amine 216; 226; 228 or 230 (1.1 equivalents) indimethylformamide (0.10 Molar) at 25° C., is added1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Nextdicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction isstirred for 14 hours. The mixture is diluted with ether, filtered andthe filtrate is washed with aqueous NaHCO₃ (2×), water (2×), and brine(2×). The organic phase is dried over MgSO₄ and then concentrated.Purification by flash column chromatography and then reexposure of theintermediate compound (1.0 equivalents) in dimethy)-formamide (0.10Molar) at 25° C., is added piperidine (1.1 equivalents). The reaction isstirred for 1 hour and is then diluted with ether, and washed withaqueous CuSO₄ (2×), water (2×), and brine (2×). The organic phase isdried over MgSO₄ and then concentrated. Purification by flash columnchromatography affords compound 226; 228; 230 or 232, respectively.scheme 24

[0337] Preparation of 234

[0338] To a stirred solution of 232 (1.0 equivalents) in acetonitrile(0.50 Molar) is added an HFEpyridine solution (0.50 M) from Aldrichchemical company. The reaction is allowed to stir for five hours and isthen condensed. The crude 234 oligomer is then resuspended in p-dioxane(0.50 Molar) to which is added a 3.0 Molar solution of NaOH (3.0equivalents). The reaction is stirred for 1 hour at 50° C. and is thenquenched with aqueous NH₄Cl (2×) and subsequently lyophilized.Purification by HPLC chromatography affords compound 234. scheme 24

PREPARATION OF PEPTOID COMBINATORIAL LIBRARIES Scheme 500

[0339] A depiction of the generation of a combinatorial library foroligopeptoid compounds is shown in scheme 500. The example uses analphabet of eight D-aldose hexose sugars (other sugars groups such asthe D/L ketoses and L-configurations of aldose hexoses, may be used) andcarries the synthesis to a degree of three or 512 compounds. (Theprocess can repeat itself to afford the library of desired size).Standard chemistry is shown and follows the reaction conditions asdescribed above herein for peptoid synthesis. The solid support used isthe standard N-(2-Aminoethyl)-3-amino-propyl glass support;amino-polystyrene resin; aminopropyl glass: isothiocyanato glass andothers as purchased from Sigma company. All supports may be with orwithout a linker extending from the amino group on the support (eg.succinate linkage. amide, ether. alkyl chain with terminal carbonactivated as free alcohol. bromide etc.).

PREPARATION OF NUCLEOTOID COMBINATORIAL LIBRARIES Scheme 550

[0340] A depiction of the generation of a combinatorial library foroligonucleotoid compounds is shown in scheme 550. The example uses analphabet of eight D-aldose hexose sugars (other sugars groups such asthe D/L ketoses and L-configurations of aldose hexoses, may be used) andcarries the synthesis to a degree of three or 512 compounds. (Theprocess can repeat itself to afford the library of desired size).Standard chemistry is shown and follows the reaction conditions asdescribed above herein for carbonucleotoid synthesis. The solid supportused is the standard N-(2-Aminoethyl)-3-amino-propyl glass support;amino-polystyrene resin; aminopropyl glass; isothiocyanato glass andothers as purchased from Sigma company. All -supports may be with orwithout a linker extending from the amino group on the support (eg.succinate linkage, amide. ether. alkyl chain with terminal carbonactivated as free alcohol. bromide etc.).

[0341] Preparation of compound 2000.

[0342] To a solution of 76 (1.0 equiv) was added methylene chloride (.1M) and benzaldehvde (1.1 equiv). and the solution was exposed to ZnCI(1.1 equiv) at 25° C. and allowed to stir for 2.5 hour. The solution isthen diluted with ether and then washed with a saturated solution ofsodium bicarbonate (2×), water (2×), brine (1×) and then dried overMgSO4. The compound is purified by flash column chromatography to yieldthe desired benzylidene.

[0343] 1. Synthesis of a C-2 differential sugar

[0344] 2. Connection of the C-2 differentiated sugar to a solid support

[0345] The benzylidene is then azeotroped with benzene (2×100 mL) andthen dried overnight under vacuum over P₂O₅. A mixture of benzylidene,dibutyl tin oxide (1.2 equiv.) and dry methanol (0.25 M) are heated atreflux for 4 h until the solution became clear and homogeneous. (Anautomatic stirring apparatus may be necessary.) The solvent is nextremoved in vacuo to give a foamy white tin complex which was thenazeotroped with benzene (2×) and dried (2 h to overnight) under vacuumover P₂O₅. Next, anhydrous DMF (0.2M) is added to redissolve the tincomplex and then CsF (1.2 equiv.) and finally Benzyl bromide (1.5equiv.) are added and then heated (40° C.) overnight. The clear solutionis partially distilled -under vacuum, (3.3 mm Hg, 75-100° C.) to obtain⅕ the original volume of solvent. Reaction mixture was then diluted withethyl acetate (2L) and washed with a small amount of water (2×) toremove cesium salts. Aqueous layer is back extracted with ethyl acetate(3×) and then recombined with the organic layer which was then driedover MgSO₄ and evaporated. Purification by flash column chromatographyyields the desired benzyl ether 2000. For related chemistry seeNagashima, N.; Ohno. M. Chemistry Letters, Chem. Soc. of Japan 1987.141.

[0346] Preparation of Compound 2010.

[0347] Procedure adopted from Johansson R.; Samuelsson; B. J. Chem.Soc., Chem. Commun., 1984, 201. To a solution of the benzylidene acetal(1 equiv) and sodium cyanoborohydride (5 equiv.) in DMF (0.125 M)containing powedered 3 angtrsom molecular sieves is addedtrifluoroacetic acid (10 equiv) and the reaction is allowed to stir at0° C. until no starting material remains. Reaction mixture is thendiluted with ethyl acetate (2L) and washed with a small amount of water(2×) and brine (2×). Aqueous layer is back extracted with ethyl acetate(3×) and then recombined with the organic layer which was then driedover MgSO₄ and evaporated. Purification by flash column chromatographyyields the desired benzyl ether 2010.

[0348] Preparation of Compound 2020.

[0349] To a solution of 2010 (1.0 equiv) was added methylene chloride(0.1 M) and benzaldehyde ( 1.1 equiv), and the solution was exposed toZnCl (1.1 equiv) at 25° C. and allowed to stir for 2.5 hour. Thesolution is then diluted with ether and then washed with a saturatedsolution of sodium bicarbonate (2×), water (2×), brine (1×) and thendried over MgSO₄. The compound is purified by flash columnchromatography to yield the desired benzylidene 2020.

[0350] Preparation of Compound 2030.

[0351] To a solution of alcohol 2020 (22.0 g, 0.1068 mol, 1.0 equiv.) inTHF (0.5 M) at 0° C., is added NaH (1.0 equiv., 35% dispersion inmineral oil) over several portions. The reaction mixture is warmed toroom temperature and stirred 1h. Next, the reaction iss cooled to 0° C.and treated with benzyl bromide (1.0 equiv.) and stirred for 1.5 h. Asaturated solution of ammonium chloride (50 mL) is added dropwise toquench the reaction mixture at 0° C. and the mixture was diluted withethyl acetate, washed with water (2×), brine (1×), dried over MgSO₄ andevaporated. Purification by flash column chromatography yields tribenzylether 2030.

[0352] Preparation of Compound 2040.

[0353] Procedure as adopted from Hanessian S.; Organic Syntheses 1987.243. To a suspension containing 1.0 equivalent of benzylidene 2030 inone molar carbon tetrachloride and 1,1,2,2-tetrachloroethane (1.5equivalent) is added 1.2 equivalents of N-bromosuccinimide and 0.5equivalents of barium carbonate. The resulting suspension is heated atthe reflux temperature of the mixture with mechanical stirring for aperiod of 2.5 hour and filtered while hot. The solution is washed withwater (3×). then dried over anhydrous sodium sulfate and evaporated.Purification by flash column chromatography yields tribenzyl ether 2040.

[0354] Preparation of Compound 2050.

[0355] To a solution of 2040 (1.0 equivalents) in methylene chloride(0.10 M), is added dilsopropylethylamine (4.0 equivalents) at 25° C. Thereaction is stirred for 5 minutes and then 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added, as preparedfrom the procedures of Sinha et al. Nucl. Acids Res. 1984, 12, 4539.After 15 minutes the reaction is

[0356] Synthesis of a C1-C2-Phosophodiester oligomer using a solidsupport

[0357] brine (1×) and is then dried (MgSO₄) and concentrated.Purification by flash column chromatography (silica, 30% ethyl acetatein petroleum ether) affords compound 2050 (as shown in scheme 2000).

[0358] Preparation of Compound 2060

[0359] To a solution of alcohol 2040 (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1h. Next, the reaction is cooled to 0° C. and exposed to thesolid support functionalized with a bromide linker or any reasonableleaving group attached (1.0 equiv.) and stirred for 2 hours. A saturatedsolution of ammonium chloride (50 mL) is added dropwise to quench thereaction mixture at 0° C. and the support was washed with ethyl acetate,1% NaOH in methanol (2×) to remove the benzoate and finally brine (1×)to give 2060. The solid support used is the standardN-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;aminopropyl glass; isothiocyanato glass and others as purchased fromSigma company. All supports may be with or without a linker extendingfrom the amino group on the support (eg. succinate linkage, amide,ether, alkyl chain with terminal carbon activated as free alcohol,bromide etc.).

[0360] 1. Synthesis of a C-3 differentiated sugar

[0361] 2. Connection of the C-3 differentiated sugar to a solid support

[0362] Preparation of Compound 2070

[0363] To a solution of 76 (1.0 equiv) was added methylene chloride (0.1M) and benzaldehyde ( 1.1 equiv), and the solution was exposed to ZnCl(1.1 equiv) at 25° C. and allowed to stir for 2.5 hour. The solution isthen diluted with ether and then washed with a saturated solution ofsodium bicarbonate (2×), water (2×), brine (1×) and then dried overMgSO₄. The compound is purified by flash column chromatography to yieldthe desired benzylidene. Procedure adopted from Johansson R.;Samuelsson; B. J. Chem. Soc., Chem. Commun., 1984, 201. To a solution ofthe benzylidene acetal (1 equiv) and sodium cyanoborohydride (5 equiv.)in DMF (0.125 M) containing powedered 3 angtrsom molecular sieves isadded trifluoroacetic acid (10 equiv) and the reaction is allowed tostir at 0° C. until no starting material remains. Reaction mixture isthen diluted with ethyl acetate (2L) and washed with a small amount ofwater (2×) and brine (2×). Aqueous layer is back extracted with ethylacetate (3×) and then recombined with the organic layer which was thendried over MgSO₄ and evaporated. Purification by flash columnchromatography yields the desired benzyl ether 2070.

[0364] Preparation of Compound 2080

[0365] To a solution of 2070 (1.0 equivalents) in methylene chloride(0.10 Molar), is added triethylamine (1.1 equivalents) at 0° C.

[0366] Subsequent addition of tertbutyldiphenylsilylchloride (1.1equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords the TBDPS ether which issubsequently carried on as follows:

[0367] The TBDPS ether is then azeotroped with benzene (2×100 mL) andthen dried overnight under vacuum over P₂O₅. A mixture of benzylidene,dibutyl tin oxide (1.2 equiv.) and dry methanol (0.25 M) are heated atreflux for 4 h until the solution became clear and homogeneous. (Anautomatic stirring apparatus may be necessary.) The solvent is nextremoved in vacuo to give a foamy white tin complex which was thenazeotroped with benzene (2×) and dried- (2h to overnight) under vacuumover P₂O₅. Next, anhydrous DMF (0.2M) is added to redissolve the tincomplex and then CsF (1.2 equiv.) and finally Benzoyl bromide for thebenzoate formation, (1.5 equiv.) are added and then heated (40° C.)overnight. The clear solution is partially distilled under vacuum, (3.3mm Hg, 75-100° C.) to obtain ⅕ the original volume of solvent. Reactionmixture was then diluted with ethyl acetate (2L) and washed with a smallamount of water (2×) to remove cesium salts. Aqueous layer is backextracted with ethyl acetate (3×) and then recombined with the organiclayer which was then dried over MgSO₄ and evaporated. Purification byflash column chromatography yields the desired benzyl ether 2080. Forrelated chemistry see Nagashima, N.; Ohno, M. Chemistry Letters, Chem.Soc. of Japan 1987, 141.

[0368] Preparation of Compound 2090

[0369] To a solution of alcohol 2080 (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1 h. Next, the reaction is cooled to 0° C. and treated withbenzyl bromide (1.0 equiv.) and stirred for 1.5 h. The compound is thentreated with tetrabutylammonium fluoride (2.0 equivalents) and allowedto stir for an additional 2 hours. A saturated solution of ammoniumchloride (50 mL) is then added dropwise to quench the reaction mixtureat 0° C. and the mixture was diluted with ethyl acetate, washed withwater (2×), brine (1×), dried over MgSO₄ and evaporated. Purification byflash column chromatography yields tribenzyl ether 2090.

[0370] Preparation of Compound 2100

[0371] To a solution of 2090 (1.0 equivalents) in methylene chloride(0.10 M), is added diisopropylethylamine (4.0 equivalents) at 25° C. Thereaction is stirred for 5 minutes and then2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added.as prepared from the procedures of Sinha et al. Nucl. Acids Res. 1984,12, 4539. After 15 minutes the reaction is complete and is next dilutedwith ether and next washed with brine (1×) and is then dried (MgSO₄) andconcentrated. Purification by flash column chromatography (silica, 30%ethyl acetate in petroleum ether) affords compound 2100 (as shown inscheme 2002).

[0372] Synthesis of a C1-C3-Phosophodiester oligomer using a solidsupport

[0373] Preparation of Compound 2110

[0374] To a solution of alcohol 2090 (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1 h. Next, the reaction is cooled to 0° C. and exposed to thesolid support functionalized with a bromide linker or any reasonableleaving group attached (1.0 equiv.) and stirred for 2 hours. A saturatedsolution of ammonium chloride (50 mL) is added dropwise to quench thereaction mixture at 0° C. and the support was washed with ethyl acetate,1% NaOH in methanol (2×) to remove the benzoate and finally brine (1×)to give 2110 The solid support used is the standardN-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;aminopropyl glass; isothiocyanato glass and others as purchased fromSigma company. All supports may be with or without a linker extendingfrom the amino group on the support (eg. succinate linkage. amide,ether, alkyl chain with terminal carbon activated as tree alcohol,bromide etc.).

[0375] Preparation of Compound 2120

[0376] To a solution of 76 (1.0 equiv) was added methylene chloride (0.1M) and benzaldehyde ( 1.1 equiv). and the solution was exposed to ZnCI (1.1 equiv) at 25° C. and allowed to stir for 2.5 hour. The solution isthen diluted with ether and then washed with a saturated solution ofsodium bicarbonate (2×), water (2×), brine (1×) and then dried overMgSO₄. The compound is purified by flash column chromatography to yieldthe desired

[0377] 1. Synthesis of a C-4 differentiated sugar

[0378] 2. Connection of the C-4 differentiated sugar to a solid support

[0379] benzylidene and carried on as follows:

[0380] To a solution of benzylidene (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1h. Next, the reaction is cooled to 0° C. and treated withbenzyl bromide (1.0 equiv.) and stirred for 1.5 h. A saturated solutionof ammonium chloride (50 mL) is then added dropwise to quench thereaction mixture at 0° C. and the mixture was diluted with ethylacetate, washed with water (2×), brine (1×), dried over MgSO₄ andevaporated. Purification by flash column chromatography yields tribenzylether 2120.

[0381] Preparation of compound 2130

[0382] Procedure adopted from Johansson R.; Samuelsson; B. J. Chem.Soc., Chem. Commun., 1984,-201. To a solution of the benzylidene acetal2120 (1 equiv) and sodium cyanoborohydride (5 equiv.) in DMF (0.125 M)containing powedered 3 angtrsom molecular sieves is addedtrifluoroacetic acid (10 equiv) and the reaction is allowed to stir at0° C. until no starting material remains. Reaction mixture is thendiluted with ethyl acetate (2L) and washed with a small amount of water(2×) and brine (2×). Aqueous layer is back extracted with ethyl acetate(3×) and then recombined with the organic layer which was then driedover MgSO₄ and evaporated. Purification by

[0383] flash column chromatography yields the desired benzyl ether 2130.

[0384] Preparation of Compound 2140

[0385] To a solution of 2130 (1.0 equivalents) in methylene chloride(0.10 Molar), is added triethylamine (1.1 equivalents) at 0° C.Subsequent addition of tertbutyldiphenylsilylchloride (1.1 equivalents)is followed by stirring for 2 hours and then the reaction is dilutedwith diethylether and washed with ammonium chloride (2×), brine (1×) andthen dried (MgSO₄) and concentrated. Purification by flash columnchromatography affords the TBDPS ether which is subsequently carried onas follows:

[0386] To a solution of TBDPS ether (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1 h. Next, the reaction is cooled to 0° C. and treated withbenzoyl bromide to afford benzoate formation (1.0 equine.) and stirredfor 1.5 h. A saturated solution of ammonium chloride (50 mL) is thenadded dropwise to quench the reaction mixture at 0° C. and the mixturewas diluted with ethyl acetate, washed with water (2×), brine (1×),dried over MgSO₄ and evaporated. Purification by flash columnchromatography yields tribenzyl ether 2140.

[0387] Preparation of Compound 2150

[0388] The compound 2140 is then treated with tetrabutylammoniumfluoride (2.0 equivalents) in THF (0.1 Molar) and allowed to stir for anadditional 2 hours at 25° C. A saturated solution of ammonium chloride(50 mL) is then added dropwise to quench the reaction mixture at 0° C.and the mixture was diluted with ethyl acetate, washed with water (2×),brine (1×), dried over MgSO₄ and evaporated. Purification by flashcolumn chromatography yields tribenzyl ether 2150.

[0389] Preparation of Compound 2160

[0390] To a solution of 2150 (1.0 equivalents) in methylene chloride(0.10 M), is added diisopropylethylamine (4.0 equivalents) at 25° C. Thereaction is stirred for 5 minutes and then 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added. as preparedfrom the procedures of Sinha et at. Nucl. Acids Res. 1984, 12, 4539.After 15 minutes the reaction is complete and is next diluted with etherand next washed with brine (1×) and is then dried (MgSO₄) andconcentrated. Purification by flash column chromatography (silica. 30%ethyl acetate in petroleum ether) affords compound 2160 (as shown inscheme 2004).

[0391] Preparation of Compound 2170

[0392] To a solution of alcohol 2150 (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (1.0 equiv., 35% dispersion in mineral oil) overseveral portions. The reaction mixture is warmed to room temperature andstirred 1h. Next, the reaction is cooled to 0° C. and exposed to thesolid support functionalized with a bromide linker or any reasonableleaving group attached (1.0 equiv.)

[0393] Synthesis of a C1-C4-Phosophodiester oligomer using a solidsupport

[0394] and stirred for 2 hours. A saturated solution of ammoniumchloride (50 mL) is added dropwise to quench the reaction mixture at 0°C. and the support was washed with ethyl acetate, 1 % NaOH in methanol(2×) to remove the benzoate and finally brine (1×) to give 2170. Thesolid support used is the standard N-(2-Aminoethyl)-3-amino-propyl glasssupport; amino-polystyrene resin; aminopropyl glass; isothiocyanatoglass and others as purchased from Sigma company. All supports may bewith or without a linker extending from the amino group on the support(eg. succinate linkage, amide, ether, alkyl chain with terminal carbonactivated as free alcohol, bromide etc.).

[0395] Preparation of Compound 3010

[0396] Procedure as described in Methods in Carbohydrate chemistry,Whistler, R., II, 1963, p. 327. A mixture of 80 g anhydrousD-glucosamine hydrochloride or D-galactosamine hydrochloride fromAldrich chemical company, in 200 mL. methanol and 20 g Dowex 50 (H+)acidic resin, is stirred at the boiling point in a round bottom flask.After 24-hr. reaction time, the resin is removed by filtration and ishedthree times with 20 ml. of methanol. The filrate and washings arecombined and concentrated to about 125 ml by rotovap. The concentrate isallowed to cool to room temperature and the product crystallizesovernight and carried on as follows:

[0397] The methyl glycoside is dissolved in chloroform (0.5 M) and toit, is added phthalic anhydride (1.5 equiv.) and the reaction mixture isallowed to reflux at 70° C. for 4 h. The product

[0398] 1. C-2 differentiated amine derivative

[0399] 3010 is then crystallized and carried onto the next step.

[0400] Preparation of Compound 3020

[0401] To a solution of alcohol 3010 (1.0 equiv.) in THF (0.5 M) at 0°C., is added NaH (3.3equiv., 35% dispersion in mineral oil) over severalportions. The reaction mixture is warmed to room temperature and stirred1 h. Next, the reaction is cooled to 0° C. and treated with benzylbromide (3.3 equiv.) and stirred for 1.5 h. A saturated solution ofammonium chloride (50 mL) is then added dropwise to quench the reactionmixture at 0° C. and the mixture was diluted with ethyl acetate, washedwith water (2×), brine (1×), dried over MgSO₄ and evaporated.Purification by flash column chromatography yields tribenzyl ether andis carried on as follows:

[0402] To a solution of tribenzyl ether in nitromethane is addedtrimethylsilyl cyanide (3.0 equivalents) and then SnCl₄ (0.02equivalents). The mixture is stirred for one hour and then an aqueoussolution of sodium acetate was added to hydrolyze the remainingtrimethylsilyl cyanide. The mixture is evaporated and the remaining oilis resuspended in dichloromethane and washed with sodium acetatesolution (1×), water (1×), brine (1×) and then dried over magnesiumsulphate and concentrated. The crude solid is then recrystallized frommethanol is next dissolved in ethanol (0.15 M) and then concentratedH₂SO₄ (0.01 equivalents-catalytic) is added. The reaction mixture isheated to 85° C. for eight hours. The solution is next concentrated invacuo and purification by flash column chromatography affords compound3020 scheme 3000.

[0403] Preparation of Compound 3030

[0404] To a solution of 3020 (1.0 equivalents) in methylene chloride(0.10 Molar), is added potassium carbonate (2.0 equivalents) at 0° C.Subsequent addition of 9-fluorenylmethyl chloroformate (FMOC-Cl, 1.2equivalents) is followed by stirring for 2 hours and then the reactionis diluted with diethylether and washed with ammonium chloride (2×),brine (1×) and then dried (MgSO₄) and concentrated. Purification byflash column chromatography affords product which is carried on asfollows:

[0405] To a solution of ester in ethanol (0.13 Molar), is added sodiumethoxide (0.3 equivalents) and the reaction mixture is stirred for twohours at room temperature. The solution is then concentrated in vacuoand purification by flash column chromatography affords compound 3030scheme 3000.

[0406] Preparation of Compound 3040

[0407] To a stirred solution of the acid 3030 ( 1.0 equivalents) and the(1.1 equivalents) in dimethylformamide (0.10 Molar) at 25° C., is added1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Nextdicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction isstirred for 2 hours. The mixture is then exposed to the solid supportand mixed for 24 hours. (The solid support used is the standardN-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;aminopropyl glass; isothiocyanato glass and others as purchased fromSigma company. All supports may be with or without a linker extendingfrom the amino group on the support (eg. succinate linkage, amide,ether, alkyl chain with terminal carbon activated as free alcohol,bromide etc.)). The mixture is then diluted with ether, washed withaqueous NaHCO₃ (2×), water (2×), and brine (2×). Next, thecompound/support (1.0 equivalents) in dimethyl-formamide (0.10 Molar) at25° C., is added piperidine (1.1 equivalents). The support is stirred orexposed for 1 hour and is then diluted with-ether, and washed withaqueous CuSO₄ (2×), water (2×), and brine (2×). The final step affordscompound 3040.

[0408] Physical Data for scheme 9.

[0409] Phosphoramidate 138 (2 diastereomers): IR, (neat) cm⁻¹: 3089,2964, 2927, 2856, 2253, 1497, 1455, 1396, 1363, 1253, 1184, 1156, 1094,1028, 978, 876, 836, 779, 735, ¹H—NM (400 MHz, C₆D₆): δ 7.34 (m, 5 H.Ph), 7.14 (m, 10 H, Ph), 4.97 (m, 4 H, CH₂Ph), 4.78 (m, 2 H, CH₂Ph),4.07-3.24 (m, 13 H, OCH, OCH₂, CH₂CN), 1. 81 (m, 2 H, CH(CH₃)₂), 1.16(m, 12 H, CH₃CH), 1.03, 1.02 (2 s, 9 H, ¹BuSi), 0.20, 0.18, 0.16, 0.15,(4 s, 6 H, Me₂Si); HRMS: C₄₃H₆₃O₇N₂PSi, Calc. (M+Cs+) : 911.3197; found:911.3185.

[0410] Naphthoylester ¹³⁶ IR, (neat) cm⁻¹: 3494, 3062, 2919, 1716, 1630,1600, 1454, 1355, 1284, 1228, 1197, 1091, 779, 736; ¹H—NMR (250 MHz,CDCI₃): δ 8.58 (s, 1 H, Ar), 8.00 (m, 2 H, Ar), 7.89 (m, 2 H, Ar), 7.59(m, 2 H, Ar), 7.32 (m, 15 H, Ph), 4.95 (m, 3 H), 4.90 (d, J=4.5 Hz, 1H), 4.69 (m, 3 H), 4.52 (dd, J=3.9, 12.0 Hz, 1 H), 3.91 (dd J=2.6, 12.0,1 H), 3.83 (d, J=8.3, 1 H), 3.70 (m, 4 H), 3.96 (m, 1 H), 2.25 (s, 1 H,OH). HRMS: C₃₉H₃₈O₇ Calc. (M+Cs+) : 751.1672; found: 751.1668.

[0411] Dimer ¹⁴² IR, (neat) cm⁻¹: 3397, 3030, 2923, 2254, 1718, 1653,1629, 1497, 1453, 1355, 1284, 1227, 1197, 1094, 1029, 780. 1H—NMR (400MHz, C₆D₆): δ 8.82 (s, 1 H, Ar), 8.26 (d, 1 H, Ar), 7.72 (m, 1 H, Ar),7.61 (m, 1 H, Ar), 7.48 (m, 1 H, Ar), 7.37-6.95 (m, 32 H, Ar, Ph),4.89-4.18 (m, 21 H, CH₂Ph, CH₂-Ar, —CH₂CH₂CN, CHCH₂—Ar and CH₂OH),3.95-3.45 (m, 13 H, CH— and CH₂-sugar), 1.71 (s, 1 H, OH); HRMS:C₁₇₀H₇₂O₅NP calc. (M+H+): 1198.4718; found: 1198.4715.

[0412] Tetramer ¹⁵⁰ IR, (neat) cm⁻¹: 3420, 3064, 2924, 2255, 1721, 1497,1455, 1357, 1278, 1028, 737. ¹H—NMR (400 MHz, CDCI₃): δ 8.41 (s, 1 H,Ar), 8.00 (m, 2 H, Ar), 7.91 (m, 2 H, Ar), 7.55 (m, 2 H, Ar), 7.30 (m,60 H, Ph), 4.93-4.05 (m, 39 H, CH₂Ph, CH₂—Ar, CH₂CH₂CN and CH₂OH),3.88-3.27 (m, 23 H, CH— and CH₂-sugar), 2.58 (s, 1 H, OH). HRMS:C₁₃₂H₁₄₀O₃₁N₃P₃ Calc. (M+Cs+) 2488.7738; found: 2488.7758.

[0413] Tetramer ¹⁵⁴ IRp, (neat) cm⁻¹: 3376, 2934, 1450, 1244, 1110,1088. ¹H—NMR (400 MHz, D₂O): δ 8.41 (s, 1 H, Ar), 8.00 (m, 2 H, Ar),7.91 (m, 2 H, Ar), 7.55 (m, 2 H, Ar), 4.93-4.05 (m, 4 H, CH₂—Ar andCH₂OH), 3.88-3.27 (m, 32 H, CH— and CH₂-sugar); HRMS: C₃₉H₅₉O₃₁P₃ Calc.(M+H+): 1117.2331; found: 1117.2350.

What is claimed is:
 1. An oligomeric carbopeptoid compound comprising carbohydrate amino acid subunits (CA's) coupled to one another via an amide linkage having a carbonyl carbon and an amido nitrogen represented by the following formula: CA₁—(CO—NH)—CA₂ wherein: CA₁ is a first carbohydrate amino acid subunit having an anomeric carbon bonded to the carbonyl carbon of said amide linkage for forming a C-glycosidic linkage therewith and CA₂ is a second carbohydrate amino acid subunit having a non-anomeric carbon bonded to the amido nitrogen of said amide linkage.
 2. In a process for synthesizing an oligomeric carbopeptoid compound, a coupling step wherein two or more carbohydrate amino acid subunits (CA's) are coupled by means of an amide linkage having a carbonyl carbon and an amido nitrogen for synthesizing said oligomeric carbopeptoid compound, said amide linkage being represented by a formula as follows: CA₁—(CO—NH)—CA₂ wherein: CA₁ is a first carbohydrate amino acid subunit having an anomeric carbon bonded to the carbonyl carbon of said amide linkage for forming a C-glycosidic linkage therewith; and CA₂ is a second carbohydrate amino acid subunit having a non-anomeric carbon bonded to the amido nitrogen of said amide linkage.
 3. A library of oligomeric carbopeptoid compounds employable for drug screening, each oligomeric carbopeptoid compound including at least two carbohydrate amino acid subunits (CA's) coupled to one another via an amide linkage having a carbonyl carbon and an amido nitrogen, said amide linkage being represented by the following formula: CA₁—(CO—NH)—CA₂ wherein: CA₁ is a first carbohydrate amino acid subunit having an anomeric carbon bonded to the carbonyl carbon of said amide linkage for forming a C-glycosidic linkage therewith; and CA₂ is a second carbohydrate amino acid subunit having a non-anomeric carbon bonded to the amido nitrogen of said amide linkage.
 4. An improved process for synthesizing a library of oligomers, the process employing an elongation step wherein subunits are coupled to one another to produce the oligomers, wherein the improvement comprises: in said elongation step the oligomer includes at least two carbohydrate amino acid subunits (CA's) coupled to one another via an amide linkage having a carbonyl carbon and an amido nitrogen represented by the following formula: CA₁—(CO—NH)—CA₂ wherein: CA₁ is a first carbohydrate amino acid subunit having an anomeric carbon bonded to the carbonyl carbon of said amide linkage for forming a C-glycosidic linkage therewith; and CA₂ is a second carbohydrate amino acid subunit having a non-anomeric carbon bonded to the amido nitrogen of said amide linkage.
 5. A derived carbohydrate amino acid having an anomeric carbon and non-anomeric carbons, said anomeric carbon being substituted with a carboxyl radical, each of said non-anomeric carbons being substituted with a radical selected from the group consisting of blocked hydroxyl, blocked amino, differentially protected amino, and hydrogen, with the proviso that at least one radical is a differentially protected amino.
 6. A derived carbohydrate amino acid having an anomeric carbon and non-anomeric carbons, said anomeric carbon being substituted with a carboxyl radical, each of said non-anomeric carbons being substituted with a radical selected from the group consisting of blocked hydroxyl, blocked amino, unprotected amino, and hydrogen, with the proviso that at least one radical is an unprotected amino and at least one radical is a blocked hydroxyl or amino.
 7. An oligomeric carbonucleotoid molecule comprising carbohydrate C-glycoside subunits (CG's) coupled to one another via a phosphodiester linkage represented by the following structure: CG₁—C₁—(O—PO(OH)—O)—CG₂ wherein: (O—PO(OH)—O) is said phosphodiester linkage; CG₁—C₁′ is a first carbohydrate C-glycoside subunit having an anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to said phosphodiester linkage; and CG₂ is a second carbohydrate C-glycoside subunit having a non-anomeric carbon bonded to said phosphodiester linkage.
 8. In a process for synthesizing an oligomeric carbonucleotoid molecule, a coupling step wherein two or more carbohydrate C-glycoside subunits (CG's) are coupled by means of a phosphodiester linkage, said phosphodiester linkage being represented by a formula as follows: CG₁—C₁′—(O—PO (OH)—O)—CG₂ wherein: (O—PO(OH)—O) is said phosphodiester linkage; CG₁—C₁′ is a first carbohydrate C-glycoside subunit having an anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to said phosphodiester linkage; and CG₂ is a second carbohydrate C-glycoside subunit having a non-anomeric carbon bonded to said phosphodiester linkage.
 9. A library of oligomeric carbonucleotoid molecules employable for drug screening, each oligomeric carbonucleotoid molecule including at least two carbohydrate C-glycoside subunits (CG's) coupled to one another by means of a phosphodiester linkage, said phosphodiester linkage being represented by a formula as follows: CG₁—C₁′—(O—PO (OH)—O)—CG₂ wherein: (O—PO(OH)—O) is said phosphodiester linkage; CG₁—C₁′ is a first carbohydrate C-glycoside subunit having an anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to said phosphodiester linkage; and CG₂ is a second carbohydrate C-glycoside subunit having a non-anomeric carbon bonded to said phosphodiester linkage.
 10. An improved process for synthesizing a library of oligomers, the process employing an elongation step wherein subunits are coupled to one another to produce the oligomers, wherein the improvement comprises: in said elongation step the oligomer is a carbonucleotoid including at least two carbohydrate C-glycoside subunits (CG's) are coupled by means of a phosphodiester linkage, said phosphodiester linkage being represented by a formula as follows: CG₁—C₁′—(O—PO (OH)—O)—CG₂ wherein: (O—PO(OH)—O) is said phosphodiester linkage; CG₁—C₁′ is a first carbohydrate C-glycoside subunit having an anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to said phosphodiester linkage; and CG₂ is a second carbohydrate C-glycoside subunit having a non-anomeric carbon bonded to said phosphodiester linkage.
 11. A derived carbohydrate C-glycoside having an anomeric carbon and non-anomeric carbons, said anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to an activated phosphite, each of said non-anomeric carbons being substituted with a radical selected from the group consisting of blocked hydroxyl, differentially protected hydroxyl, and hydrogen, with the proviso that at least one radical is a differentially protected hydroxyl.
 12. A derived carbohydrate C-glycoside having an anomeric carbon and non-anomeric carbons, said anomeric carbon forming a C-glycosidic bond with a carbon C₁′, said carbon C₁′ being bonded to an activated phosphite, each of said non-anomeric carbons being substituted with a radical selected from the group consisting of blocked hydroxyl, unprotected hydroxyl, and hydrogen, with the proviso that at least one radical is an unprotected hydroxyl and at least one radical is a blocked hydroxyl. 